Autoimmune Hepatitis and Stellate Cells: An Insight into the Role of Autophagy

doi:10.2174/0929867326666190402120231
摘要

自身免疫性肝炎是肝脏的一种坏死炎症过程，以T细胞、巨噬细胞和浆细胞侵入门脉周围实质的界面肝炎为特征。在这个过程中，会分泌多种细胞因子，肝组织发生纤维化，导致肝细胞凋亡。自噬是一种互补机制，抑制细胞内病原体，固有免疫系统不能提供有效的内吞。具有特殊再生特征的肝细胞通常处于静止状态，自噬控制着多余产物的积累，因此肝脏是研究自噬的基础模型。在代谢性疾病中，肝脏自噬功能障碍导致肝细胞中受损细胞器、错误折叠蛋白和脂质过多的积累。在这篇综述中，我们介绍了自身免疫性肝炎与自噬信号的关联。我们还讨论了自噬的一些基因和蛋白质，它们在肝星状细胞激活中的调节作用，以及脂质和酪氨酸激酶在肝纤维化中的重要性。为了全面综述自噬在自身免疫性肝炎中的调控作用，本文还涵盖了自噬在自身免疫性肝炎中的通路分析。
关键词: 自体免疫性肝炎，星状细胞，自噬，细胞信号传导，自体免疫性疾病，AIH，慢性肝炎。
« Previous
[1] 
Manns, M.P.; Czaja, A.J.; Gorham, J.D.; Krawitt, E.L.; Mieli-Vergani, G.; Vergani, D.; Vierling, J.M. American association for the study of liver diseases. Diagnosis and management of autoimmune hepatitis. Hepatology,  2010, 51(6), 2193-2213.
[http://dx.doi.org/10.1002/hep.23584 ] [PMID:  20513004] 
[2] 
Liberal, R.; Grant, C.R.; Longhi, M.S.; Mieli-Vergani, G.; Vergani, D. Diagnostic criteria of autoimmune hepatitis. Autoimmun. Rev.,  2014, 13(4-5), 435-440.
[http://dx.doi.org/10.1016/j.autrev.2013.11.009 ] [PMID:  24418295] 
[3] 
Doumtsis, P.; Oikonomou, T.; Goulis, I.; Zachou, K.; Dalekos, G.; Cholongitas, E. Type 1 autoimmune hepatitis presenting with severe autoimmune neutropenia. Ann. Gastroenterol.,  2018, 31(1), 123-126.
[http://dx.doi.org/10.20524/aog.2017.0186 ] [PMID:  29333079] 
[4] 
Amin, K.; Rasool, A.H.; Hattem, A.; Al-Karboly, T.A.; Taher, T.E.; Bystrom, J. Autoantibody profiles in autoimmune hepatitis and chronic hepatitis C identifies similarities in patients with severe disease. World J. Gastroenterol.,  2017, 23(8), 1345-1352.
[http://dx.doi.org/10.3748/wjg.v23.i8.1345 ] [PMID:  28293081] 
[5] 
Lowe, D.; John, S. Autoimmune hepatitis: appraisal of current treatment guidelines. World J. Hepatol.,  2018, 10(12), 911-923.
[http://dx.doi.org/10.4254/wjh.v10.i12.911 ] [PMID:  30631396] 
[6] 
Floreani, A.; Restrepo-Jiménez, P.; Secchi, M.F.; De Martin, S.; Leung, P.S.C.; Krawitt, E.; Bowlus, C.L.; Gershwin, M.E.; Anaya, J-M. Etiopathogenesis of autoimmune hepatitis. J. Autoimmun.,  2018, 95, 133-143.
[http://dx.doi.org/10.1016/j.jaut.2018.10.020 ] [PMID:  30385083] 
[7] 
Zhang, J.Y.; Zhang, Z.; Lin, F.; Zou, Z.S.; Xu, R.N.; Jin, L.; Fu, J.L.; Shi, F.; Shi, M.; Wang, H.F.; Wang, F.S. Interleukin-17-producing CD4(+) T cells increase with severity of liver damage in patients with chronic hepatitis B. Hepatology,  2010, 51(1), 81-91.
[http://dx.doi.org/10.1002/hep.23273 ] [PMID:  19842207] 
[8] 
Christen, U.; Hintermann, E. Immunopathogenic mechanisms of autoimmune hepatitis: how much do we know from animal models? Int. J. Mol. Sci.,  2016, 17(12), 2007.
[http://dx.doi.org/10.3390/ijms17122007 ] [PMID:  27916939] 
[9] 
Liberal, R.; Mieli-Vergani, G.; Vergani, D. Autoimmune hepatitis: From mechanisms to therapy. Rev Clin Esp,  2016, 216(7), 372-383.
[http://dx.doi.org/10.1016/j.rce.2016.04.003 ] [PMID:  27161382] 
[10] 
Liberal, R.; Vergani, D.; Mieli-Vergani, G. Update on autoimmune hepatitis. J. Clin. Transl. Hepatol.,  2015, 3(1), 42-52.
[http://dx.doi.org/10.14218/JCTH.2014.00032 ] [PMID:  26357634] 
[11] 
Tsuchida, T.; Friedman, S.L. Mechanisms of hepatic stellate cell activation. Nat. Rev. Gastroenterol. Hepatol.,  2017, 14(7), 397-411.
[http://dx.doi.org/10.1038/nrgastro.2017.38 ] [PMID:  28487545] 
[12] 
Higashi, T.; Friedman, S.L.; Hoshida, Y. Hepatic stellate cells as key target in liver fibrosis. Adv. Drug Deliv. Rev.,  2017, 121, 27-42.
[http://dx.doi.org/10.1016/j.addr.2017.05.007 ] [PMID:  28506744] 
[13] 
Fleisher, T.A.; Shearer, W.T.; Frew, A.J.; Schroeder, H.W., Jr; Weyand, C.M. Clinical immunology, principles and practice (expert consult-online and print), 4: Clinical immunology; Elsevier Health Sciences, 2013. 
[14] 
Anthony, P.P.; Ishak, K.G.; Nayak, N.C.; Poulsen, H.E.; Scheuer, P.J.; Sobin, L.H. The morphology of cirrhosis. Recommendations on definition, nomenclature and classification by a working group sponsored by the World Health Organization. J. Clin. Pathol.,  1978, 31(5), 395-414.
[http://dx.doi.org/10.1136/jcp.31.5.395 ] [PMID:  649765] 
[15] 
Wells, R.G. Cellular sources of extracellular matrix in hepatic fibrosis. Clin. Liver Dis.,  2008, 12(4), 759-768  viii..
[http://dx.doi.org/10.1016/j.cld.2008.07.008 ] [PMID: 18984465] 
[16] 
Friedman, S.L. Mechanisms of hepatic fibrogenesis. Gastroenterology,  2008, 134(6), 1655-1669.
[http://dx.doi.org/10.1053/j.gastro.2008.03.003 ] [PMID:  18471545] 
[17] 
Pinzani, M.; Marra, F. Cytokine receptors and signaling in hepatic stellate cells. Semin. Liver Dis.,  2001, 21(3), 397-416.
[http://dx.doi.org/10.1055/s-2001-17554 ] [PMID:  11586468] 
[18] 
Guo, C.Y.; Wu, J.Y.; Wu, Y.B.; Zhong, M.Z.; Lu, H.M. Effects of endothelin-1 on hepatic stellate cell proliferation, collagen synthesis and secretion, intracellular free calcium concentration. World J. Gastroenterol.,  2004, 10(18), 2697-2700.
[http://dx.doi.org/10.3748/wjg.v10.i18.2697 ] [PMID:  15309721] 
[19] 
Gonzalo, T.; Beljaars, L.; van de Bovenkamp, M.; Temming, K.; van Loenen, A-M.; Reker-Smit, C.; Meijer, D.K.F.; Lacombe, M.; Opdam, F.; Kéri, G.; Örfi, L.; Poelstra, K.; Kok, R.J. Local inhibition of liver fibrosis by specific delivery of a platelet-derived growth factor kinase inhibitor to hepatic stellate cells. J. Pharmacol. Exp. Ther.,  2007, 321(3), 856-865.
[http://dx.doi.org/10.1124/jpet.106.114496 ] [PMID:  17369283] 
[20] 
Marra, F.; Romanelli, R.G.; Giannini, C.; Failli, P.; Pastacaldi, S.; Arrighi, M.C.; Pinzani, M.; Laffi, G.; Montalto, P.; Gentilini, P. Monocyte chemotactic protein-1 as a chemoattractant for human hepatic stellate cells. Hepatology,  1999, 29(1), 140-148.
[http://dx.doi.org/10.1002/hep.510290107 ] [PMID:  9862860] 
[21] 
Gentilini, A.; Marra, F.; Gentilini, P.; Pinzani, M. Phosphatidylinositol-3 kinase and extracellular signal-regulated kinase mediate the chemotactic and mitogenic effects of insulin-like growth factor-I in human hepatic stellate cells. J. Hepatol.,  2000, 32(2), 227-234.
[http://dx.doi.org/10.1016/S0168-8278(00)80067-7 ] [PMID:  10707862] 
[22] 
Deshmane, S.L.; Kremlev, S.; Amini, S.; Sawaya, B.E. Monocyte chemoattractant protein-1 (MCP-1): an overview. J. Interferon Cytokine Res.,  2009, 29(6), 313-326.
[http://dx.doi.org/10.1089/jir.2008.0027 ] [PMID:  19441883] 
[23] 
DeLeve, L.D. Liver sinusoidal endothelial cells in hepatic fibrosis. Hepatology,  2015, 61(5), 1740-1746.
[http://dx.doi.org/10.1002/hep.27376 ] [PMID:  25131509] 
[24] 
Luo, J.; Liang, Y.; Kong, F.; Qiu, J.; Liu, X.; Chen, A.; Luxon, B.A.; Wu, H.W.; Wang, Y. Vascular endothelial growth factor promotes the activation of hepatic stellate cells in chronic schistosomiasis. Immunol. Cell Biol.,  2017, 95(4), 399-407.
[http://dx.doi.org/10.1038/icb.2016.109 ] [PMID:  27808086] 
[25] 
Jager, J.; Aparicio-Vergara, M.; Aouadi, M. Liver innate immune cells and insulin resistance: the multiple facets of Kupffer cells. J. Intern. Med.,  2016, 280(2), 209-220.
[http://dx.doi.org/10.1111/joim.12483 ] [PMID:  26864622] 
[26] 
Moreno, M.; Bataller, R. Cytokines and renin-angiotensin system signaling in hepatic fibrosis. Clin. Liver Dis.,  2008, 12(4), 825-852 ix..
[http://dx.doi.org//10.1016/j.cld.2008.07.013] [PMID: 18984469] 
[27] 
Bataller, R.; Sancho-Bru, P.; Ginès, P.; Lora, J.M.; Al-Garawi, A.; Solé, M.; Colmenero, J.; Nicolás, J.M.; Jiménez, W.; Weich, N.; Gutiérrez-Ramos, J.C.; Arroyo, V.; Rodés, J. Activated human hepatic stellate cells express the renin-angiotensin system and synthesize angiotensin II. Gastroenterology,  2003, 125(1), 117-125.
[http://dx.doi.org/10.1016/S0016-5085(03)00695-4 ] [PMID:  12851877] 
[28] 
Choi, S.S.; Syn, W-K.; Karaca, G.F.; Omenetti, A.; Moylan, C.A.; Witek, R.P.; Agboola, K.M.; Jung, Y.; Michelotti, G.A.; Diehl, A.M. Leptin promotes the myofibroblastic phenotype in hepatic stellate cells by activating the hedgehog pathway. J. Biol. Chem.,  2010, 285(47), 36551-36560.
[http://dx.doi.org/10.1074/jbc.M110.168542 ] [PMID:  20843817] 
[29] 
Manns, M.P.; Taubert, R. Treatment of autoimmune hepatitis. Clin. Liver Dis. (Hoboken),  2014, 3(1), 15-17.
[http://dx.doi.org/10.1002/cld.306 ] [PMID:  30992882] 
[30] 
Cropley, A.; Weltman, M. The use of immunosuppression in autoimmune hepatitis: a current literature review. Clin. Mol. Hepatol.,  2017, 23(1), 22-26.
[http://dx.doi.org/10.3350/cmh.2016.0089 ] [PMID:  28288505] 
[31] 
Terziroli Beretta-Piccoli, B.; Mieli-Vergani, G.; Vergani, D. Autoimmune hepatitis: Standard treatment and systematic review of alternative treatments. World J. Gastroenterol.,  2017, 23(33), 6030-6048.
[http://dx.doi.org/10.3748/wjg.v23.i33.6030 ] [PMID:  28970719] 
[32] 
Doycheva, I.; Watt, K.D.; Gulamhusein, A.F. Autoimmune hepatitis: current and future therapeutic options. Liver Int.,  2019, 39(6), 1002-1013.
[http://dx.doi.org/10.1111/liv.14062 ] [PMID:  30716203] 
[33] 
Janmohamed, A.; Hirschfield, G.M. Autoimmune hepatitis and complexities in management. Frontline Gastroenterol.,  2019, 10(1), 77-87.
[http://dx.doi.org/10.1136/flgastro-2018-101015 ] [PMID:  30651962] 
[34] 
Taubert, R.; Hupa-Breier, K.L.; Jaeckel, E.; Manns, M.P. Novel therapeutic targets in autoimmune hepatitis. J. Autoimmun.,  2018, 95, 34-46.
[http://dx.doi.org/10.1016/j.jaut.2018.10.022 ] [PMID:  30401504] 
[35] 
Jang, Y.J.; Kim, J.H.; Byun, S. Modulation of autophagy for controlling immunity. Cells,  2019, 8(2), 138.
[http://dx.doi.org/10.3390/cells8020138 ] [PMID:  30744138] 
[36] 
Schulze, R.J.; Drižytė, K.; Casey, C.A.; McNiven, M.A. Hepatic lipophagy: new insights into autophagic catabolism of lipid droplets in the liver. Hepatol Commun,  2017, 1(5), 359-369.
[http://dx.doi.org/10.1002/hep4.1056 ] [PMID:  29109982] 
[37] 
Hernández-Gea, V.; Ghiassi-Nejad, Z.; Rozenfeld, R.; Gordon, R.; Fiel, M.I.; Yue, Z.; Czaja, M.J.; Friedman, S.L. Autophagy releases lipid that promotes fibrogenesis by activated hepatic stellate cells in mice and in human tissues. Gastroenterology,  2012, 142(4), 938-946.
[http://dx.doi.org/10.1053/j.gastro.2011.12.044 ] [PMID:  22240484] 
[38] 
Ravanan, P.; Srikumar, I.F.; Talwar, P. Autophagy: the spotlight for cellular stress responses. Life Sci.,  2017, 188, 53-67.
[http://dx.doi.org/10.1016/j.lfs.2017.08.029 ] [PMID:  28866100] 
[39] 
Glick, D.; Barth, S.; Macleod, K.F. Autophagy: cellular and molecular mechanisms. J. Pathol.,  2010, 221(1), 3-12.
[http://dx.doi.org/10.1002/path.2697 ] [PMID:  20225336] 
[40] 
Galluzzi, L.; Baehrecke, E.H.; Ballabio, A.; Boya, P.; Bravo-San Pedro, J.M.; Cecconi, F.; Choi, A.M.; Chu, C.T.; Codogno, P.; Colombo, M.I.; Cuervo, A.M.; Debnath, J.; Deretic, V.; Dikic, I.; Eskelinen, E.L.; Fimia, G.M.; Fulda, S.; Gewirtz, D.A.; Green, D.R.; Hansen, M.; Harper, J.W.; Jäättelä, M.; Johansen, T.; Juhasz, G.; Kimmelman, A.C.; Kraft, C.; Ktistakis, N.T.; Kumar, S.; Levine, B.; Lopez-Otin, C.; Madeo, F.; Martens, S.; Martinez, J.; Melendez, A.; Mizushima, N.; Münz, C.; Murphy, L.O.; Penninger, J.M.; Piacentini, M.; Reggiori, F.; Rubinsztein, D.C.; Ryan, K.M.; Santambrogio, L.; Scorrano, L.; Simon, A.K.; Simon, H.U.; Simonsen, A.; Tavernarakis, N.; Tooze, S.A.; Yoshimori, T.; Yuan, J.; Yue, Z.; Zhong, Q.; Kroemer, G. Molecular definitions of autophagy and related processes. EMBO J.,  2017, 36(13), 1811-1836.
[http://dx.doi.org/10.15252/embj.201796697 ] [PMID:  28596378] 
[41] 
Singh, R.; Kaushik, S.; Wang, Y.; Xiang, Y.; Novak, I.; Komatsu, M.; Tanaka, K.; Cuervo, A.M.; Czaja, M.J. Autophagy regulates lipid metabolism. Nature,  2009, 458(7242), 1131-1135.
[http://dx.doi.org/10.1038/nature07976 ] [PMID:  19339967] 
[42] 
Madrigal-Matute, J.; Cuervo, A.M. Regulation of liver metabolism by autophagy. Gastroenterology,  2016, 150(2), 328-339.
[http://dx.doi.org/10.1053/j.gastro.2015.09.042 ] [PMID:  26453774] 
[43] 
Nixon, R.A. The role of autophagy in neurodegenerative disease. Nat. Med.,  2013, 19(8), 983-997.
[http://dx.doi.org/10.1038/nm.3232 ] [PMID:  23921753] 
[44] 
Budini, M.; Buratti, E.; Morselli, E.; Criollo, A. Autophagy and its impact on neurodegenerative diseases: new roles for TDP-43 and C9orf72. Front. Mol. Neurosci.,  2017, 10, 170.
[http://dx.doi.org/10.3389/fnmol.2017.00170 ] [PMID:  28611593] 
[45] 
Thurston, T.L.M.; Ryzhakov, G.; Bloor, S.; von Muhlinen, N.; Randow, F. The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria. Nat. Immunol.,  2009, 10(11), 1215-1221.
[http://dx.doi.org/10.1038/ni.1800 ] [PMID:  19820708] 
[46] 
Bah, A.; Vergne, I. Macrophage autophagy and bacterial infections. Front. Immunol.,  2017, 8, 1483.
[http://dx.doi.org/10.3389/fimmu.2017.01483 ] [PMID:  29163544] 
[47] 
Dash, S.; Chava, S.; Aydin, Y.; Chandra, P.K.; Ferraris, P.; Chen, W.; Balart, L.A.; Wu, T.; Garry, R.F. Hepatitis C virus infection induces autophagy as a prosurvival mechanism to alleviate hepatic er-stress response. Viruses,  2016, 8(5), 150.
[http://dx.doi.org/10.3390/v8050150 ] [PMID:  27223299] 
[48] 
Ke, P-Y.; Chen, S.S.L. Autophagy in hepatitis C virus-host interactions: potential roles and therapeutic targets for liver-associated diseases. World J. Gastroenterol.,  2014, 20(19), 5773-5793.
[http://dx.doi.org/10.3748/wjg.v20.i19.5773 ] [PMID:  24914338] 
[49] 
White, E. The role for autophagy in cancer. J. Clin. Invest.,  2015, 125(1), 42-46.
[http://dx.doi.org/10.1172/JCI73941 ] [PMID:  25654549] 
[50] 
Galluzzi, L.; Pietrocola, F.; Bravo-San Pedro, J.M.; Amaravadi, R.K.; Baehrecke, E.H.; Cecconi, F.; Codogno, P.; Debnath, J.; Gewirtz, D.A.; Karantza, V.; Kimmelman, A.; Kumar, S.; Levine, B.; Maiuri, M.C.; Martin, S.J.; Penninger, J.; Piacentini, M.; Rubinsztein, D.C.; Simon, H-U.; Simonsen, A.; Thorburn, A.M.; Velasco, G.; Ryan, K.M.; Kroemer, G. Autophagy in malignant transformation and cancer progression. EMBO J.,  2015, 34(7), 856-880.
[http://dx.doi.org/10.15252/embj.201490784 ] [PMID:  25712477] 
[51] 
Chung, S.J.; Nagaraju, G.P.; Nagalingam, A.; Muniraj, N.; Kuppusamy, P.; Walker, A.; Woo, J.; Győrffy, B.; Gabrielson, E.; Saxena, N.K.; Sharma, D. ADIPOQ/adiponectin induces cytotoxic autophagy in breast cancer cells through STK11/LKB1-mediated activation of the AMPK-ULK1 axis. Autophagy,  2017, 13(8), 1386-1403.
[http://dx.doi.org/10.1080/15548627.2017.1332565 ] [PMID:  28696138] 
[52] 
Ezaki, J.; Matsumoto, N.; Takeda-Ezaki, M.; Komatsu, M.; Takahashi, K.; Hiraoka, Y.; Taka, H.; Fujimura, T.; Takehana, K.; Yoshida, M.; Iwata, J.; Tanida, I.; Furuya, N.; Zheng, D-M.; Tada, N.; Tanaka, K.; Kominami, E.; Ueno, T. Liver autophagy contributes to the maintenance of blood glucose and amino acid levels. Autophagy,  2011, 7(7), 727-736.
[http://dx.doi.org/10.4161/auto.7.7.15371 ] [PMID:  21471734] 
[53] 
Puleston, D.J.; Simon, A.K. Autophagy in the immune system. Immunology,  2014, 141(1), 1-8.
[http://dx.doi.org/10.1111/imm.12165 ] [PMID:  23991647] 
[54] 
Jia, W.; He, M-X.; McLeod, I.X.; Guo, J.; Ji, D.; He, Y-W. Autophagy regulates T lymphocyte proliferation through selective degradation of the cell-cycle inhibitor CDKN1B/p27Kip1. Autophagy,  2015, 11(12), 2335-2345.
[http://dx.doi.org/10.1080/15548627.2015.1110666 ] [PMID:  26569626] 
[55] 
McLeod, I.X.; Jia, W.; He, Y-W. The contribution of autophagy to lymphocyte survival and homeostasis. Immunol. Rev.,  2012, 249(1), 195-204.
[http://dx.doi.org/10.1111/j.1600-065X.2012.01143.x ] [PMID:  22889223] 
[56] 
Weindel, C.G.; Richey, L.J.; Bolland, S.; Mehta, A.J.; Kearney, J.F.; Huber, B.T. B cell autophagy mediates TLR7-dependent autoimmunity and inflammation. Autophagy,  2015, 11(7), 1010-1024.
[http://dx.doi.org/10.1080/15548627.2015.1052206 ] [PMID:  26120731] 
[57] 
Bhattacharya, A.; Eissa, N.T. Autophagy and autoimmunity crosstalks. Front. Immunol.,  2013, 4, 88.
[http://dx.doi.org/10.3389/fimmu.2013.00088 ] [PMID:  23596443] 
[58] 
Nedjic, J.; Aichinger, M.; Emmerich, J.; Mizushima, N.; Klein, L. Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance. Nature,  2008, 455(7211), 396-400.
[http://dx.doi.org/10.1038/nature07208 ] [PMID:  18701890] 
[59] 
Fujishima, Y.; Nishiumi, S.; Masuda, A.; Inoue, J.; Nguyen, N.M.T.; Irino, Y.; Komatsu, M.; Tanaka, K.; Kutsumi, H.; Azuma, T.; Yoshida, M. Autophagy in the intestinal epithelium reduces endotoxin-induced inflammatory responses by inhibiting NF-κB activation. Arch. Biochem. Biophys.,  2011, 506(2), 223-235.
[http://dx.doi.org/10.1016/j.abb.2010.12.009 ] [PMID:  21156154] 
[60] 
Unger, R.H.; Clark, G.O.; Scherer, P.E.; Orci, L. Lipid homeostasis, lipotoxicity and the metabolic syndrome. Biochim. Biophys. Acta,  2010, 1801(3), 209-214.
[http://dx.doi.org/10.1016/j.bbalip.2009.10.006 ] [PMID:  19948243] 
[61] 
Hintermann, E.; Ehser, J.; Bayer, M.; Pfeilschifter, J.M.; Christen, U. Mechanism of autoimmune hepatic fibrogenesis induced by an adenovirus encoding the human liver autoantigen cytochrome P450 2D6. J. Autoimmun.,  2013, 44, 49-60.
[http://dx.doi.org/10.1016/j.jaut.2013.05.001 ] [PMID:  23809878] 
[62] 
Komiya, K.; Uchida, T.; Ueno, T.; Koike, M.; Abe, H.; Hirose, T.; Kawamori, R.; Uchiyama, Y.; Kominami, E.; Fujitani, Y.; Watada, H. Free fatty acids stimulate autophagy in pancreatic β-cells via JNK pathway. Biochem. Biophys. Res. Commun.,  2010, 401(4), 561-567.
[http://dx.doi.org/10.1016/j.bbrc.2010.09.101 ] [PMID:  20888798] 
[63] 
Thoen, L.F.; Guimarães, E.L.; Grunsven, L.A. Autophagy: a new player in hepatic stellate cell activation. Autophagy,  2012, 8(1), 126-128.
[http://dx.doi.org/10.4161/auto.8.1.18105 ] [PMID:  22082960] 
[64] 
Yamada, M.; Blaner, W.S.; Soprano, D.R.; Dixon, J.L.; Kjeldbye, H.M.; Goodman, D.S. Biochemical characteristics of isolated rat liver stellate cells. Hepatology,  1987, 7(6), 1224-1229.
[http://dx.doi.org/10.1002/hep.1840070609 ] [PMID:  2824313] 
[65] 
Hara, T.; Nakamura, K.; Matsui, M.; Yamamoto, A.; Nakahara, Y.; Suzuki-Migishima, R.; Yokoyama, M.; Mishima, K.; Saito, I.; Okano, H.; Mizushima, N. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature,  2006, 441(7095), 885-889.
[http://dx.doi.org/10.1038/nature04724 ] [PMID:  16625204] 
[66] 
Suzuki, K.; Kirisako, T.; Kamada, Y.; Mizushima, N.; Noda, T.; Ohsumi, Y. The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation. EMBO J.,  2001, 20(21), 5971-5981.
[http://dx.doi.org/10.1093/emboj/20.21.5971 ] [PMID:  11689437] 
[67] 
Dreux, M.; Gastaminza, P.; Wieland, S.F.; Chisari, F.V. The autophagy machinery is required to initiate hepatitis C virus replication. Proc. Natl. Acad. Sci. USA,  2009, 106(33), 14046-14051.
[http://dx.doi.org/10.1073/pnas.0907344106 ] [PMID:  19666601] 
[68] 
Jounai, N.; Takeshita, F.; Kobiyama, K.; Sawano, A.; Miyawaki, A.; Xin, K.Q.; Ishii, K.J.; Kawai, T.; Akira, S.; Suzuki, K.; Okuda, K. The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc. Natl. Acad. Sci. USA,  2007, 104(35), 14050-14055.
[http://dx.doi.org/10.1073/pnas.0704014104 ] [PMID:  17709747] 
[69] 
Matsunaga, K.; Morita, E.; Saitoh, T.; Akira, S.; Ktistakis, N.T.; Izumi, T.; Noda, T.; Yoshimori, T. Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L. J. Cell Biol.,  2010, 190(4), 511-521.
[http://dx.doi.org/10.1083/jcb.200911141 ] [PMID:  20713597] 
[70] 
Fogel, A.I.; Dlouhy, B.J.; Wang, C.; Ryu, S.W.; Neutzner, A.; Hasson, S.A.; Sideris, D.P.; Abeliovich, H.; Youle, R.J. Role of membrane association and Atg14-dependent phosphorylation in beclin-1-mediated autophagy. Mol. Cell. Biol.,  2013, 33(18), 3675-3688.
[http://dx.doi.org/10.1128/MCB.00079-13 ] [PMID:  23878393] 
[71] 
Nishimura, T.; Kaizuka, T.; Cadwell, K.; Sahani, M.H.; Saitoh, T.; Akira, S.; Virgin, H.W.; Mizushima, N. FIP200 regulates targeting of Atg16L1 to the isolation membrane. EMBO Rep.,  2013, 14(3), 284-291.
[http://dx.doi.org/10.1038/embor.2013.6 ] [PMID:  23392225] 
[72] 
Homer, C.R.; Richmond, A.L.; Rebert, N.A.; Achkar, J.P.; McDonald, C. ATG16L1 and NOD2 interact in an autophagy-dependent antibacterial pathway implicated in Crohn’s disease pathogenesis. Gastroenterology, 2010,
	139(5), 1630-1641, 1641.e1-1641.e2., 
[http://dx.doi.org/10.1053/j.gastro.2010.07.006] [PMID: 20637199] 
[73] 
Sorbara, M.T.; Ellison, L.K.; Ramjeet, M.; Travassos, L.H.; Jones, N.L.; Girardin, S.E.; Philpott, D.J. The protein ATG16L1 suppresses inflammatory cytokines induced by the intracellular sensors Nod1 and Nod2 in an autophagy-independent manner. Immunity,  2013, 39(5), 858-873.
[http://dx.doi.org/10.1016/j.immuni.2013.10.013 ] [PMID:  24238340] 
[74] 
Gaugel, A.; Bakula, D.; Hoffmann, A.; Proikas-Cezanne, T. Defining regulatory and phosphoinositide-binding sites in the human WIPI-1 β-propeller responsible for autophagosomal membrane localization downstream of mTORC1 inhibition. J. Mol. Signal.,  2012, 7(1), 16.
[http://dx.doi.org/10.1186/1750-2187-7-16 ] [PMID:  23088497] 
[75] 
Radoshevich, L.; Murrow, L.; Chen, N.; Fernandez, E.; Roy, S.; Fung, C.; Debnath, J. ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death. Cell,  2010, 142(4), 590-600.
[http://dx.doi.org/10.1016/j.cell.2010.07.018 ] [PMID:  20723759] 
[76] 
Sou, Y.S.; Tanida, I.; Komatsu, M.; Ueno, T.; Kominami, E. Phosphatidylserine in addition to phosphatidylethanolamine is an in vitro target of the mammalian Atg8 modifiers, LC3, GABARAP, and GATE-16. J. Biol. Chem.,  2006, 281(6), 3017-3024.
[http://dx.doi.org/10.1074/jbc.M505888200 ] [PMID:  16303767] 
[77] 
Tanida, I.; Yamasaki, M.; Komatsu, M.; Ueno, T. The FAP motif within human ATG7, an autophagy-related E1-like enzyme, is essential for the E2-substrate reaction of LC3 lipidation. Autophagy,  2012, 8(1), 88-97.
[http://dx.doi.org/10.4161/auto.8.1.18339 ] [PMID:  22170151] 
[78] 
Young, A.R.; Chan, E.Y.; Hu, X.W.; Köchl, R.; Crawshaw, S.G.; High, S.; Hailey, D.W.; Lippincott-Schwartz, J.; Tooze, S.A. Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J. Cell Sci.,  2006, 119(Pt 18), 3888-3900.
[http://dx.doi.org/10.1242/jcs.03172 ] [PMID:  16940348] 
[79] 
Crighton, D.; Wilkinson, S.; O’Prey, J.; Syed, N.; Smith, P.; Harrison, P.R.; Gasco, M.; Garrone, O.; Crook, T.; Ryan, K.M. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell,  2006, 126(1), 121-134.
[http://dx.doi.org/10.1016/j.cell.2006.05.034 ] [PMID:  16839881] 
[80] 
Singh, S.B.; Davis, A.S.; Taylor, G.A.; Deretic, V. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science,  2006, 313(5792), 1438-1441.
[http://dx.doi.org/10.1126/science.1129577 ] [PMID:  16888103] 
[81] 
Hubert, V.; Peschel, A.; Langer, B.; Gröger, M.; Rees, A.; Kain, R. LAMP-2 is required for incorporating syntaxin-17 into autophagosomes and for their fusion with lysosomes. Biol. Open,  2016, 5(10), 1516-1529.
[http://dx.doi.org/10.1242/bio.018648 ] [PMID:  27628032] 
[82] 
Lu, B.; Nakamura, T.; Inouye, K.; Li, J.; Tang, Y.; Lundbäck, P.; Valdes-Ferrer, S.I.; Olofsson, P.S.; Kalb, T.; Roth, J.; Zou, Y.; Erlandsson-Harris, H.; Yang, H.; Ting, J.P.; Wang, H.; Andersson, U.; Antoine, D.J.; Chavan, S.S.; Hotamisligil, G.S.; Tracey, K.J. Novel role of PKR in inflammasome activation and HMGB1 release. Nature,  2012, 488(7413), 670-674.
[http://dx.doi.org/10.1038/nature11290 ] [PMID:  22801494] 
[83] 
Mitoma, H.; Hanabuchi, S.; Kim, T.; Bao, M.; Zhang, Z.; Sugimoto, N.; Liu, Y.J. The DHX33 RNA helicase senses cytosolic RNA and activates the NLRP3 inflammasome. Immunity,  2013, 39(1), 123-135.
[http://dx.doi.org/10.1016/j.immuni.2013.07.001 ] [PMID:  23871209] 
[84] 
Inohara, N.; Koseki, T.; del Peso, L.; Hu, Y.; Yee, C.; Chen, S.; Carrio, R.; Merino, J.; Liu, D.; Ni, J.; Núñez, G. Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor-kappaB. J. Biol. Chem.,  1999, 274(21), 14560-14567.
[http://dx.doi.org/10.1074/jbc.274.21.14560 ] [PMID:  10329646] 
[85] 
Ren, Y.; Liu, S.F.; Nie, L.; Cai, S.Y.; Chen, J. Involvement of ayu NOD2 in NF-kappaB and MAPK signaling pathways: Insights into functional conservation of NOD2 in antibacterial innate immunity. Zool. Res.,  2019, 40(2), 77-88.
[http://dx.doi.org/10.24272/j.issn.2095-8137.2018.066 ] [PMID:  29872030] 
[86] 
Itakura, E.; Kishi-Itakura, C.; Mizushima, N. The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes. Cell,  2012, 151(6), 1256-1269.
[http://dx.doi.org/10.1016/j.cell.2012.11.001 ] [PMID:  23217709] 
[87] 
Chen, D.; Fan, W.; Lu, Y.; Ding, X.; Chen, S.; Zhong, Q. A mammalian autophagosome maturation mechanism mediated by TECPR1 and the Atg12-Atg5 conjugate. Mol. Cell,  2012, 45(5), 629-641.
[http://dx.doi.org/10.1016/j.molcel.2011.12.036 ] [PMID:  22342342] 
[88] 
Mizushima, N.; Yoshimori, T.; Levine, B. Methods in mammalian autophagy research. Cell,  2010, 140(3), 313-326.
[http://dx.doi.org/10.1016/j.cell.2010.01.028 ] [PMID:  20144757] 
[89] 
Noda, T.; Matsunaga, K.; Taguchi-Atarashi, N.; Yoshimori, T. Regulation of membrane biogenesis in autophagy via PI3P dynamics. Semin. Cell Dev. Biol.,  2010, 21(7), 671-676.
[http://dx.doi.org/10.1016/j.semcdb.2010.04.002 ] [PMID:  20403452] 
[90] 
Morris, D.H.; Yip, C.K.; Shi, Y.; Chait, B.T.; Wang, Q.J. BECLIN 1-VPS34 complex architecture: understanding the nuts and bolts of therapeutic targets. Front. Biol. (Beijing),  2015, 10(5), 398-426.
[http://dx.doi.org/10.1007/s11515-015-1374-y ] [PMID:  26692106] 
[91] 
Komatsu, M.; Waguri, S.; Koike, M.; Sou, Y.S.; Ueno, T.; Hara, T.; Mizushima, N.; Iwata, J.; Ezaki, J.; Murata, S.; Hamazaki, J.; Nishito, Y.; Iemura, S.; Natsume, T.; Yanagawa, T.; Uwayama, J.; Warabi, E.; Yoshida, H.; Ishii, T.; Kobayashi, A.; Yamamoto, M.; Yue, Z.; Uchiyama, Y.; Kominami, E.; Tanaka, K. Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell,  2007, 131(6), 1149-1163.
[http://dx.doi.org/10.1016/j.cell.2007.10.035 ] [PMID:  18083104] 
[92] 
Luo, M.X.M.; Wong, S.H.; Chan, M.T.V.; Yu, L.; Yu, S.S.B.; Wu, F.; Xiao, Z.; Wang, X.; Zhang, L.; Cheng, A.S.L.; Ng, S.S.M.; Chan, F.K.L.; Cho, C.H.; Yu, J.; Sung, J.J.Y.; Wu, W.K.K. Autophagy mediates HBx-induced nuclear factor-κB activation and release of IL-6, IL-8, and CXCL2 in hepatocytes. J. Cell. Physiol.,  2015, 230(10), 2382-2389.
[http://dx.doi.org/10.1002/jcp.24967 ] [PMID:  25708728] 
[93] 
Nakatogawa, H. Two ubiquitin-like conjugation systems that mediate membrane formation during autophagy. Essays Biochem.,  2013, 55, 39-50.
[http://dx.doi.org/10.1042/bse0550039 ] [PMID:  24070470] 
[94] 
Papinski, D.; Schuschnig, M.; Reiter, W.; Wilhelm, L.; Barnes, C.A.; Maiolica, A.; Hansmann, I.; Pfaffenwimmer, T.; Kijanska, M.; Stoffel, I.; Lee, S.S.; Brezovich, A.; Lou, J.H.; Turk, B.E.; Aebersold, R.; Ammerer, G.; Peter, M.; Kraft, C. Early steps in autophagy depend on direct phosphorylation of Atg9 by the Atg1 kinase. Mol. Cell,  2014, 53(3), 471-483.
[http://dx.doi.org/10.1016/j.molcel.2013.12.011 ] [PMID:  24440502] 
[95] 
Mari, M.; Griffith, J.; Rieter, E.; Krishnappa, L.; Klionsky, D.J.; Reggiori, F. An Atg9-containing compartment that functions in the early steps of autophagosome biogenesis. J. Cell Biol.,  2010, 190(6), 1005-1022.
[http://dx.doi.org/10.1083/jcb.200912089 ] [PMID:  20855505] 
[96] 
Backues, S.K.; Orban, D.P.; Bernard, A.; Singh, K.; Cao, Y.; Klionsky, D.J. Atg23 and Atg27 act at the early stages of Atg9 trafficking in S. cerevisiae. Traffic,  2015, 16(2), 172-190.
[http://dx.doi.org/10.1111/tra.12240 ] [PMID:  25385507] 
[97] 
Levine, B.; Kroemer, G. Autophagy in the pathogenesis of disease. Cell,  2008, 132(1), 27-42.
[http://dx.doi.org/10.1016/j.cell.2007.12.018 ] [PMID:  18191218] 
[98] 
Komatsu, M.; Waguri, S.; Ueno, T.; Iwata, J.; Murata, S.; Tanida, I.; Ezaki, J.; Mizushima, N.; Ohsumi, Y.; Uchiyama, Y.; Kominami, E.; Tanaka, K.; Chiba, T. Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice. J. Cell Biol.,  2005, 169(3), 425-434.
[http://dx.doi.org/10.1083/jcb.200412022 ] [PMID:  15866887] 
[99] 
Xiao, Y.; Liu, H.; Yu, J.; Zhao, Z.; Xiao, F.; Xia, T.; Wang, C.; Li, K.; Deng, J.; Guo, Y.; Chen, S.; Chen, Y.; Guo, F. MAPK1/3 regulate hepatic lipid metabolism via ATG7-dependent autophagy. Autophagy,  2016, 12(3), 592-593.
[http://dx.doi.org/10.1080/15548627.2015.1135282 ] [PMID:  26760678] 
[100] 
Yeganeh, B.; Hashemi, M.; de Serres, F.J.; Los, M.J.; Ghavami, S. Different faces of hepatocellular carcinoma as a health threat in 21st century. Hepat. Mon.,  2013, 13(2)e9308
[http://dx.doi.org/10.5812/hepatmon.9308 ] [PMID:  23613688] 
[101] 
Salminen, A.; Kaarniranta, K.; Kauppinen, A. Beclin 1 interactome controls the crosstalk between apoptosis, autophagy and inflammasome activation: impact on the aging process. Ageing Res. Rev.,  2013, 12(2), 520-534.
[http://dx.doi.org/10.1016/j.arr.2012.11.004 ] [PMID:  23220384] 
[102] 
Zhou, X.J.; Zhang, H. Autophagy in immunity: implications in etiology of autoimmune/autoinflammatory diseases. Autophagy,  2012, 8(9), 1286-1299.
[http://dx.doi.org/10.4161/auto.21212 ] [PMID:  22878595] 
[103] 
Hwang, S.; Maloney, N.S.; Bruinsma, M.W.; Goel, G.; Duan, E.; Zhang, L.; Shrestha, B.; Diamond, M.S.; Dani, A.; Sosnovtsev, S.V.; Green, K.Y.; Lopez-Otin, C.; Xavier, R.J.; Thackray, L.B.; Virgin, H.W. Nondegradative role of Atg5-Atg12/Atg16L1 autophagy protein complex in antiviral activity of interferon gamma. Cell Host Microbe,  2012, 11(4), 397-409.
[http://dx.doi.org/10.1016/j.chom.2012.03.002 ] [PMID:  22520467] 
[104] 
Dreux, M.; Chisari, F.V. Viruses and the autophagy machinery. Cell Cycle,  2010, 9(7), 1295-1307.
[http://dx.doi.org/10.4161/cc.9.7.11109 ] [PMID:  20305376] 
[105] 
Travassos, L.H.; Carneiro, L.A.; Ramjeet, M.; Hussey, S.; Kim, Y-G.; Magalhães, J.G.; Yuan, L.; Soares, F.; Chea, E.; Le Bourhis, L.; Boneca, I.G.; Allaoui, A.; Jones, N.L.; Nuñez, G.; Girardin, S.E.; Philpott, D.J. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat. Immunol.,  2010, 11(1), 55-62.
[http://dx.doi.org/10.1038/ni.1823 ] [PMID:  19898471] 
[106] 
Correa, R.G.; Milutinovic, S.; Reed, J.C. Roles of NOD1 (NLRC1) and NOD2 (NLRC2) in innate immunity and inflammatory diseases. Biosci. Rep.,  2012, 32(6), 597-608.
[http://dx.doi.org/10.1042/BSR20120055 ] [PMID:  22908883] 
[107] 
Park, J-H.; Kim, Y-G.; McDonald, C.; Kanneganti, T-D.; Hasegawa, M.; Body-Malapel, M.; Inohara, N.; Núñez, G. RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs. J. Immunol.,  2007, 178(4), 2380-2386.
[http://dx.doi.org/10.4049/jimmunol.178.4.2380 ] [PMID:  17277144] 
[108] 
Chauhan, S.; Mandell, M.A.; Deretic, V. Mechanism of action of the tuberculosis and Crohn disease risk factor IRGM in autophagy. Autophagy,  2016, 12(2), 429-431.
[http://dx.doi.org/10.1080/15548627.2015.1084457 ] [PMID:  26313894] 
[109] 
Parkes, M.; Barrett, J.C.; Prescott, N.J.; Tremelling, M.; Anderson, C.A.; Fisher, S.A.; Roberts, R.G.; Nimmo, E.R.; Cummings, F.R.; Soars, D.; Drummond, H.; Lees, C.W.; Khawaja, S.A.; Bagnall, R.; Burke, D.A.; Todhunter, C.E.; Ahmad, T.; Onnie, C.M.; McArdle, W.; Strachan, D.; Bethel, G.; Bryan, C.; Lewis, C.M.; Deloukas, P.; Forbes, A.; Sanderson, J.; Jewell, D.P.; Satsangi, J.; Mansfield, J.C.; Cardon, L.; Mathew, C.G. Wellcome trust case control consortium. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn’s disease susceptibility. Nat. Genet.,  2007, 39(7), 830-832.
[http://dx.doi.org/10.1038/ng2061 ] [PMID:  17554261] 
[110] 
McCarroll, S.A.; Huett, A.; Kuballa, P.; Chilewski, S.D.; Landry, A.; Goyette, P.; Zody, M.C.; Hall, J.L.; Brant, S.R.; Cho, J.H.; Duerr, R.H.; Silverberg, M.S.; Taylor, K.D.; Rioux, J.D.; Altshuler, D.; Daly, M.J.; Xavier, R.J. Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn’s disease. Nat. Genet.,  2008, 40(9), 1107-1112.
[http://dx.doi.org/10.1038/ng.215 ] [PMID:  19165925] 
[111] 
Brest, P.; Lapaquette, P.; Mograbi, B.; Darfeuille-Michaud, A.; Hofman, P. Risk predisposition for Crohn disease: a “ménage à trois” combining IRGM allele, miRNA and xenophagy. Autophagy,  2011, 7(7), 786-787.
[http://dx.doi.org/10.4161/auto.7.7.15595 ] [PMID:  21508684] 
[112] 
Villani, A.C.; Lemire, M.; Fortin, G.; Louis, E.; Silverberg, M.S.; Collette, C.; Baba, N.; Libioulle, C.; Belaiche, J.; Bitton, A.; Gaudet, D.; Cohen, A.; Langelier, D.; Fortin, P.R.; Wither, J.E.; Sarfati, M.; Rutgeerts, P.; Rioux, J.D.; Vermeire, S.; Hudson, T.J.; Franchimont, D. Common variants in the NLRP3 region contribute to Crohn’s disease susceptibility. Nat. Genet.,  2009, 41(1), 71-76.
[http://dx.doi.org/10.1038/ng.285 ] [PMID:  19098911] 
[113] 
Igor’V, M.; Andreev, D.N. Role of mutations in NOD2/CARD15, ATG16L1, and IRGM in the pathogenesis of Crohn’s disease. Inflamm. Bowel Dis.,  2014, 1, 5.
[114] 
Canbay, A.; Bechmann, L.P.; Best, J.; Jochum, C.; Treichel, U.; Gerken, G. Crohn’s disease-induced non-alcoholic fatty liver disease (NAFLD) sensitizes for severe acute hepatitis B infection and liver failure. Z. Gastroenterol.,  2006, 44(3), 245-248.
[http://dx.doi.org/10.1055/s-2006-926502 ] [PMID:  16514570] 
[115] 
Chong, Z.Z. mTOR: a novel therapeutic target for diseases of multiple systems. Curr. Drug Targets,  2015, 16(10), 1107-1132.
[http://dx.doi.org/10.2174/1389450116666150408103448 ] [PMID:  25850623] 
[116] 
Perl, A. mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging. Ann. N. Y. Acad. Sci.,  2015, 1346(1), 33-44.
[http://dx.doi.org/10.1111/nyas.12756 ] [PMID:  25907074] 
[117] 
Matter, M.S.; Decaens, T.; Andersen, J.B.; Thorgeirsson, S.S. Targeting the mTOR pathway in hepatocellular carcinoma: current state and future trends. J. Hepatol.,  2014, 60(4), 855-865.
[http://dx.doi.org/10.1016/j.jhep.2013.11.031 ] [PMID:  24308993] 
[118] 
Chen, J.S.; Wang, Q.; Fu, X.H.; Huang, X-H.; Chen, X.L.; Cao, L.Q.; Chen, L.Z.; Tan, H.X.; Li, W.; Bi, J.; Zhang, L.J. Involvement of PI3K/PTEN/AKT/mTOR pathway in invasion and metastasis in hepatocellular carcinoma: Association with MMP-9. Hepatol. Res.,  2009, 39(2), 177-186.
[http://dx.doi.org/10.1111/j.1872-034X.2008.00449.x ] [PMID:  19208038] 
[119] 
Kerkar, N.; Dugan, C.; Rumbo, C.; Morotti, R.A.; Gondolesi, G.; Shneider, B.L.; Emre, S. Rapamycin successfully treats post-transplant autoimmune hepatitis. Am. J. Transplant.,  2005, 5(5), 1085-1089.
[http://dx.doi.org/10.1111/j.1600-6143.2005.00801.x ] [PMID:  15816890] 
[120] 
Song, G.; Ouyang, G.; Bao, S. The activation of Akt/PKB signaling pathway and cell survival. J. Cell. Mol. Med.,  2005, 9(1), 59-71.
[http://dx.doi.org/10.1111/j.1582-4934.2005.tb00337.x ] [PMID:  15784165] 
[121] 
Schmelzle, T.; Hall, M.N. TOR, a central controller of cell growth. Cell,  2000, 103(2), 253-262.
[http://dx.doi.org/10.1016/S0092-8674(00)00117-3 ] [PMID:  11057898] 
[122] 
Mahadevan, D.; Powis, G.; Mash, E.A.; George, B.; Gokhale, V.M.; Zhang, S.; Shakalya, K.; Du-Cuny, L.; Berggren, M.; Ali, M.A.; Jana, U.; Ihle, N.; Moses, S.; Franklin, C.; Narayan, S.; Shirahatti, N.; Meuillet, E.J. Discovery of a novel class of AKT pleckstrin homology domain inhibitors. Mol. Cancer Ther.,  2008, 7(9), 2621-2632.
[http://dx.doi.org/10.1158/1535-7163.MCT-07-2276 ] [PMID:  18790745] 
[123] 
Manning, B.D.; Cantley, L.C. AKT/PKB signaling: navigating downstream. Cell,  2007, 129(7), 1261-1274.
[http://dx.doi.org/10.1016/j.cell.2007.06.009 ] [PMID:  17604717] 
[124] 
Datta, S.R.; Brunet, A.; Greenberg, M.E. Cellular survival: a play in three Akts. Genes Dev.,  1999, 13(22), 2905-2927.
[http://dx.doi.org/10.1101/gad.13.22.2905 ] [PMID:  10579998] 
[125] 
Ghavami, S.; Hashemi, M.; Kadkhoda, K.; Alavian, S.M.; Bay, G.H.; Los, M. Apoptosis in liver diseases--detection and therapeutic applications. Med. Sci. Monit.,  2005, 11(11), RA337-RA345.
[PMID:  16258409] 
[126] 
Martindale, J.L.; Holbrook, N.J. Cellular response to oxidative stress: signaling for suicide and survival. J. Cell. Physiol.,  2002, 192(1), 1-15.
[http://dx.doi.org/10.1002/jcp.10119 ] [PMID:  12115731] 
[127] 
Alessi, D.R.; Andjelkovic, M.; Caudwell, B.; Cron, P.; Morrice, N.; Cohen, P.; Hemmings, B.A. Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J.,  1996, 15(23), 6541-6551.
[http://dx.doi.org/10.1002/j.1460-2075.1996.tb01045.x ] [PMID:  8978681] 
[128] 
Lee, J.V.; Carrer, A.; Shah, S.; Snyder, N.W.; Wei, S.; Venneti, S.; Worth, A.J.; Yuan, Z.F.; Lim, H.W.; Liu, S.; Jackson, E.; Aiello, N.M.; Haas, N.B.; Rebbeck, T.R.; Judkins, A.; Won, K.J.; Chodosh, L.A.; Garcia, B.A.; Stanger, B.Z.; Feldman, M.D.; Blair, I.A.; Wellen, K.E. Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation. Cell Metab.,  2014, 20(2), 306-319.
[http://dx.doi.org/10.1016/j.cmet.2014.06.004 ] [PMID:  24998913] 
[129] 
Jain, M.V.; Shareef, A.; Likus, W.; Cieślar-Pobuda, A.; Ghavami, S.; Łos, M.J. Inhibition of miR301 enhances Akt-mediated cell proliferation by accumulation of PTEN in nucleus and its effects on cell-cycle regulatory proteins. Oncotarget,  2016, 7(15), 20953-20965.
[http://dx.doi.org/10.18632/oncotarget.7996 ] [PMID:  26967567] 
[130] 
Czaja, A.J. Autoimmune hepatitis. Part A: pathogenesis. Expert Rev. Gastroenterol. Hepatol.,  2007, 1(1), 113-128.
[http://dx.doi.org/10.1586/17474124.1.1.113 ] [PMID:  19072440] 
[131] 
Bortoluci, K.R.; Medzhitov, R. Control of infection by pyroptosis and autophagy: role of TLR and NLR. Cell. Mol. Life Sci.,  2010, 67(10), 1643-1651.
[http://dx.doi.org/10.1007/s00018-010-0335-5 ] [PMID:  20229126] 
[132] 
Baccala, R.; Hoebe, K.; Kono, D.H.; Beutler, B.; Theofilopoulos, A.N. TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity. Nat. Med.,  2007, 13(5), 543-551.
[http://dx.doi.org/10.1038/nm1590 ] [PMID:  17479100] 
[133] 
Krieg, A.M.; Vollmer, J. Toll-like receptors 7, 8, and 9: linking innate immunity to autoimmunity. Immunol. Rev.,  2007, 220(1), 251-269.
[http://dx.doi.org/10.1111/j.1600-065X.2007.00572.x ] [PMID:  17979852] 
[134] 
Kanno, A.; Tanimura, N.; Ishizaki, M.; Ohko, K.; Motoi, Y.; Onji, M.; Fukui, R.; Shimozato, T.; Yamamoto, K.; Shibata, T.; Sano, S.; Sugahara-Tobinai, A.; Takai, T.; Ohto, U.; Shimizu, T.; Saitoh, S.; Miyake, K. Targeting cell surface TLR7 for therapeutic intervention in autoimmune diseases. Nat. Commun.,  2015, 6, 6119.
[http://dx.doi.org/10.1038/ncomms7119 ] [PMID:  25648980] 
[135] 
Delgado, M.A.; Elmaoued, R.A.; Davis, A.S.; Kyei, G.; Deretic, V. Toll-like receptors control autophagy. EMBO J.,  2008, 27(7), 1110-1121.
[http://dx.doi.org/10.1038/emboj.2008.31 ] [PMID:  18337753] 
[136] 
Shi, C.S.; Kehrl, J.H. MyD88 and Trif target Beclin 1 to trigger autophagy in macrophages. J. Biol. Chem.,  2008, 283(48), 33175-33182.
[http://dx.doi.org/10.1074/jbc.M804478200 ] [PMID:  18772134] 
[137] 
Delgado, M.A.; Deretic, V. Toll-like receptors in control of immunological autophagy. Cell Death Differ.,  2009, 16(7), 976-983.
[http://dx.doi.org/10.1038/cdd.2009.40 ] [PMID:  19444282] 
[138] 
Liu, B.; Dai, J.; Zheng, H.; Stoilova, D.; Sun, S.; Li, Z. Cell surface expression of an endoplasmic reticulum resident heat shock protein gp96 triggers MyD88-dependent systemic autoimmune diseases. Proc. Natl. Acad. Sci. USA,  2003, 100(26), 15824-15829.
[http://dx.doi.org/10.1073/pnas.2635458100 ] [PMID:  14668429] 
[139] 
Sanjuan, M.A.; Dillon, C.P.; Tait, S.W.G.; Moshiach, S.; Dorsey, F.; Connell, S.; Komatsu, M.; Tanaka, K.; Cleveland, J.L.; Withoff, S.; Green, D.R. Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis. Nature,  2007, 450, 1253.
[http://dx.doi.org/10.1038/nature06421 ] [PMID:  18097414] 
[140] 
Ghavami, S.; Cunnington, R.H.; Gupta, S.; Yeganeh, B.; Filomeno, K.L.; Freed, D.H.; Chen, S.; Klonisch, T.; Halayko, A.J.; Ambrose, E.; Singal, R.; Dixon, I.M. Autophagy is a regulator of TGF-β1-induced fibrogenesis in primary human atrial myofibroblasts. Cell Death Dis.,  2015, 6e1696
[http://dx.doi.org/10.1038/cddis.2015.36 ] [PMID:  25789971] 
[141] 
Olsen, A.L.; Bloomer, S.A.; Chan, E.P.; Gaça, M.D.A.; Georges, P.C.; Sackey, B.; Uemura, M.; Janmey, P.A.; Wells, R.G. Hepatic stellate cells require a stiff environment for myofibroblastic differentiation. Am. J. Physiol. Gastrointest. Liver Physiol.,  2011, 301(1), G110-G118.
[http://dx.doi.org/10.1152/ajpgi.00412.2010 ] [PMID:  21527725] 
[142] 
Hsieh, C.C.; Hung, C.H.; Lu, L.; Qian, S. Hepatic immune tolerance induced by hepatic stellate cells. World J. Gastroenterol.,  2015, 21(42), 11887-11892.
[http://dx.doi.org/10.3748/wjg.v21.i42.11887 ] [PMID:  26576077] 
[143] 
Winau, F.; Hegasy, G.; Weiskirchen, R.; Weber, S.; Cassan, C.; Sieling, P.A.; Modlin, R.L.; Liblau, R.S.; Gressner, A.M.; Kaufmann, S.H. Ito cells are liver-resident antigen-presenting cells for activating T cell responses. Immunity,  2007, 26(1), 117-129.
[http://dx.doi.org/10.1016/j.immuni.2006.11.011 ] [PMID:  17239632] 
[144] 
Friedman, S.L. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J. Biol. Chem.,  2000, 275(4), 2247-2250.
[http://dx.doi.org/10.1074/jbc.275.4.2247 ] [PMID:  10644669] 
[145] 
Weinreich, M.A.; Lintmaer, I.; Wang, L.; Liggitt, H.D.; Harkey, M.A.; Blau, C.A. Growth factor receptors as regulators of hematopoiesis. Blood,  2006, 108(12), 3713-3721.
[http://dx.doi.org/10.1182/blood-2006-01-012278 ] [PMID:  16902155] 
[146] 
Hinz, B. The extracellular matrix and transforming growth factor-β1: Tale of a strained relationship. Matrix Biol.,  2015, 47, 54-65.
[http://dx.doi.org/10.1016/j.matbio.2015.05.006 ] [PMID:  25960420] 
[147] 
Qureshi, O.S.; Bon, H.; Twomey, B.; Holdsworth, G.; Ford, K.; Bergin, M.; Huang, L.; Muzylak, M.; Healy, L.J.; Hurdowar, V.; Johnson, T.S. An immunofluorescence assay for extracellular matrix components highlights the role of epithelial cells in producing a stable, fibrillar extracellular matrix. Biol. Open,  2017, 6(10), 1423-1433.
[http://dx.doi.org/10.1242/bio.025866 ] [PMID:  29032370] 
[148] 
Cattaneo, F.; Guerra, G.; Parisi, M.; De Marinis, M.; Tafuri, D.; Cinelli, M.; Ammendola, R. Cell-surface receptors transactivation mediated by g protein-coupled receptors. Int. J. Mol. Sci.,  2014, 15(11), 19700-19728.
[http://dx.doi.org/10.3390/ijms151119700 ] [PMID:  25356505] 
[149] 
Parola, M.; Marra, F.; Pinzani, M. Myofibroblast - like cells and liver fibrogenesis: Emerging concepts in a rapidly moving scenario. Mol. Aspects Med.,  2008, 29(1-2), 58-66.
[http://dx.doi.org/10.1016/j.mam.2007.09.002 ] [PMID:  18022682] 
[150] 
Li, J.T.; Liao, Z.X.; Ping, J.; Xu, D.; Wang, H. Molecular mechanism of hepatic stellate cell activation and antifibrotic therapeutic strategies. J. Gastroenterol.,  2008, 43(6), 419-428.
[http://dx.doi.org/10.1007/s00535-008-2180-y ] [PMID:  18600385] 
[151] 
Kisseleva, T.; Uchinami, H.; Feirt, N.; Quintana-Bustamante, O.; Segovia, J.C.; Schwabe, R.F.; Brenner, D.A. Bone marrow-derived fibrocytes participate in pathogenesis of liver fibrosis. J. Hepatol.,  2006, 45(3), 429-438.
[http://dx.doi.org/10.1016/j.jhep.2006.04.014 ] [PMID:  16846660] 
[152] 
Cassiman, D.; Libbrecht, L.; Desmet, V.; Denef, C.; Roskams, T. Hepatic stellate cell/myofibroblast subpopulations in fibrotic human and rat livers. J. Hepatol.,  2002, 36(2), 200-209.
[http://dx.doi.org/10.1016/S0168-8278(01)00260-4 ] [PMID:  11830331] 
[153] 
Gupta, S.S.; Zeglinski, M.R.; Rattan, S.G.; Landry, N.M.; Ghavami, S.; Wigle, J.T.; Klonisch, T.; Halayko, A.J.; Dixon, I.M. Inhibition of autophagy inhibits the conversion of cardiac fibroblasts to cardiac myofibroblasts. Oncotarget,  2016, 7(48), 78516-78531.
[http://dx.doi.org/10.18632/oncotarget.12392 ] [PMID:  27705938] 
[154] 
Ghavami, S.; Cunnington, R.H.; Yeganeh, B.; Davies, J.J.; Rattan, S.G.; Bathe, K.; Kavosh, M.; Los, M.J.; Freed, D.H.; Klonisch, T.; Pierce, G.N.; Halayko, A.J.; Dixon, I.M. Autophagy regulates trans fatty acid-mediated apoptosis in primary cardiac myofibroblasts. Biochim. Biophys. Acta,  2012, 1823(12), 2274-2286.
[http://dx.doi.org/10.1016/j.bbamcr.2012.09.008 ] [PMID:  23026405] 
[155] 
Bonner, J.C. Regulation of PDGF and its receptors in fibrotic diseases. Cytokine Growth Factor Rev.,  2004, 15(4), 255-273.
[http://dx.doi.org/10.1016/j.cytogfr.2004.03.006 ] [PMID:  15207816] 
[156] 
Paul, M.K.; Mukhopadhyay, A.K. Tyrosine kinase - Role and significance in Cancer. Int. J. Med. Sci.,  2004, 1(2), 101-115.
[http://dx.doi.org/10.7150/ijms.1.101 ] [PMID:  15912202] 
[157] 
Kolios, G.; Valatas, V.; Kouroumalis, E. Role of Kupffer cells in the pathogenesis of liver disease. World J. Gastroenterol.,  2006, 12(46), 7413-7420.
[http://dx.doi.org/10.3748/wjg.v12.i46.7413 ] [PMID:  17167827] 
[158] 
Duarte, S.; Baber, J.; Fujii, T.; Coito, A.J. Matrix metalloproteinases in liver injury, repair and fibrosis. Matrix Biol.,  2015, 44-46, 147-156.
[http://dx.doi.org/10.1016/j.matbio.2015.01.004] [PMID:  25599939] 
[159] 
Nikitin, A.; Egorov, S.; Daraselia, N.; Mazo, I. Pathway studio--the analysis and navigation of molecular networks. Bioinformatics,  2003, 19(16), 2155-2157.
[http://dx.doi.org/10.1093/bioinformatics/btg290 ] [PMID:  14594725] 
[160] 
Rachfal, A.W.; Brigstock, D.R. Connective tissue growth factor (CTGF/CCN2) in hepatic fibrosis. Hepatol. Res.,  2003, 26(1), 1-9.
[http://dx.doi.org/10.1016/s1386-6346(03)00115-3 ] [PMID:  12787797] 
[161] 
DeLeve, L.D. Liver sinusoidal endothelial cells and liver regeneration. J. Clin. Invest.,  2013, 123(5), 1861-1866.
[http://dx.doi.org/10.1172/JCI66025 ] [PMID:  23635783] 
[162] 
Ghatak, S.; Biswas, A.; Dhali, G.K.; Chowdhury, A.; Boyer, J.L.; Santra, A. Oxidative stress and hepatic stellate cell activation are key events in arsenic induced liver fibrosis in mice. Toxicol. Appl. Pharmacol.,  2011, 251(1), 59-69.
[http://dx.doi.org/10.1016/j.taap.2010.11.016 ] [PMID:  21134390] 
[163] 
Gandhi, C.R. Oxidative stress and hepatic stellate cells: a paradoxical relationship. Trends Cell Mol. Biol.,  2012, 7, 1-10.
[PMID:  27721591] 
[164] 
March, S.; Graupera, M.; Rosa Sarrias, M.; Lozano, F.; Pizcueta, P.; Bosch, J.; Engel, P. Identification and functional characterization of the hepatic stellate cell CD38 cell surface molecule. Am. J. Pathol.,  2007, 170(1), 176-187.
[http://dx.doi.org/10.2353/ajpath.2007.051212 ] [PMID:  17200192] 
[165] 
Sanz, S.; Pucilowska, J.B.; Liu, S.; Rodríguez-Ortigosa, C.M.; Lund, P.K.; Brenner, D.A.; Fuller, C.R.; Simmons, J.G.; Pardo, A.; Martínez-Chantar, M.L.; Fagin, J.A.; Prieto, J. Expression of insulin-like growth factor I by activated hepatic stellate cells reduces fibrogenesis and enhances regeneration after liver injury. Gut,  2005, 54(1), 134-141.
[http://dx.doi.org/10.1136/gut.2003.024505 ] [PMID:  15591519] 
[166] 
Nishizawa, H.; Iguchi, G.; Fukuoka, H.; Takahashi, M.; Suda, K.; Bando, H.; Matsumoto, R.; Yoshida, K.; Odake, Y.; Ogawa, W.; Takahashi, Y. IGF-I induces senescence of hepatic stellate cells and limits fibrosis in a p53-dependent manner. Sci. Rep.,  2016, 6, 34605.
[http://dx.doi.org/10.1038/srep34605 ] [PMID:  27721459] 
[167] 
Kalogeris, T.; Baines, C.P.; Krenz, M.; Korthuis, R.J. Cell biology of ischemia/reperfusion injury. Int. Rev. Cell Mol. Biol.,  2012, 298, 229-317.
[http://dx.doi.org/10.1016/B978-0-12-394309-5.00006-7 ] [PMID:  22878108] 
[168] 
Dooley, S.; ten Dijke, P. TGF-β in progression of liver disease. Cell Tissue Res.,  2012, 347(1), 245-256.
[http://dx.doi.org/10.1007/s00441-011-1246-y ] [PMID:  22006249] 
[169] 
Yokomori, H.; Oda, M.; Yoshimura, K.; Nagai, T.; Ogi, M.; Nomura, M.; Ishii, H. Vascular endothelial growth factor increases fenestral permeability in hepatic sinusoidal endothelial cells. Liver Int.,  2003, 23(6), 467-475.
[http://dx.doi.org/10.1111/j.1478-3231.2003.00880.x ] [PMID:  14986821] 
[170] 
Cattoretti, G.; Angelin-Duclos, C.; Shaknovich, R.; Zhou, H.; Wang, D.; Alobeid, B. PRDM1/Blimp-1 is expressed in human B-lymphocytes committed to the plasma cell lineage. J. Pathol.,  2005, 206(1), 76-86.
[http://dx.doi.org/10.1002/path.1752 ] [PMID:  15772984] 
[171] 
Tucci, M.; Stucci, S.; Savonarola, A.; Resta, L.; Cives, M.; Rossi, R.; Silvestris, F. An imbalance between Beclin-1 and p62 expression promotes the proliferation of myeloma cells through autophagy regulation. Exp. Hematol.,  2014, 42(10), 897-908.e1.
[http://dx.doi.org/10.1016/j.exphem.2014.06.005 ] [PMID:  24971696] 
[172] 
Yuan, J.; Yu, M.; Li, H-H.; Long, Q.; Liang, W.; Wen, S.; Wang, M.; Guo, H-P.; Cheng, X.; Liao, Y-H. Autophagy contributes to IL-17-induced plasma cell differentiation in experimental autoimmune myocarditis. Int. Immunopharmacol.,  2014, 18(1), 98-105.
[http://dx.doi.org/10.1016/j.intimp.2013.11.008 ] [PMID:  24269624] 
[173] 
Valaperti, A.; Eriksson, U. The role of IL-17 in experimental autoimmune myocarditis In: Th 17 Cells: Role in Inflammation and Autoimmune Disease, Quesniaux, V.;Ryffel, B.; Padova, F.D. (Eds.); Springer Link, 2009, 115-
126.. 
[http://dx.doi.org/10.1007/978-3-7643-8681-8_10] 
[174] 
Eriksson, U. The role of IL-17 in experimental autoimmune myocarditis In: IL-17, IL-22 and their producing cells: role
in inflammation and autoimmunity, Quesniaux, V.; Ryffel,
B.; Padova, F.D. (Eds.); Springer Link; , 2013. 165-175. 
[http://dx.doi.org/10.1007/978-3-0348-0522-3_12] 
[175] 
Kimura, A.; Ishida, Y.; Wada, T.; Hisaoka, T.; Morikawa, Y.; Sugaya, T.; Mukaida, N.; Kondo, T. The absence of interleukin-6 enhanced arsenite-induced renal injury by promoting autophagy of tubular epithelial cells with aberrant extracellular signal-regulated kinase activation. Am. J. Pathol.,  2010, 176(1), 40-50.
[http://dx.doi.org/10.2353/ajpath.2010.090146 ] [PMID:  20008137] 
[176] 
Hamzawy, M.; Gouda, S.A.A.; Rashid, L.; Attia Morcos, M.; Shoukry, H.; Sharawy, N. The cellular selection between apoptosis and autophagy: roles of vitamin D, glucose and immune response in diabetic nephropathy. Endocrine,  2017, 58(1), 66-80.
[http://dx.doi.org/10.1007/s12020-017-1402-6 ] [PMID:  28889337] 
[177] 
Moore, K.W.; de Waal Malefyt, R.; Coffman, R.L.; O’Garra, A. Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol.,  2001, 19, 683-765.
[http://dx.doi.org/10.1146/annurev.immunol.19.1.683 ] [PMID:  11244051] 
[178] 
Park, H.J.; Lee, S.J.; Kim, S.H.; Han, J.; Bae, J.; Kim, S.J.; Park, C.G.; Chun, T. IL-10 inhibits the starvation induced autophagy in macrophages via class I phosphatidylinositol 3-kinase (PI3K) pathway. Mol. Immunol.,  2011, 48(4), 720-727.
[http://dx.doi.org/10.1016/j.molimm.2010.10.020 ] [PMID:  21095008] 
[179] 
Efimova, O.V.; Kelley, T.W. Induction of granzyme B expression in T-cell receptor/CD28-stimulated human regulatory T cells is suppressed by inhibitors of the PI3K-mTOR pathway. BMC Immunol.,  2009, 10, 59-59.
[http://dx.doi.org/10.1186/1471-2172-10-59 ] [PMID:  19930596] 
[180] 
Laplante, M.; Sabatini, D.M. mTOR signaling in growth control and disease. Cell,  2012, 149(2), 274-293.
[http://dx.doi.org/10.1016/j.cell.2012.03.017 ] [PMID:  22500797] 
[181] 
Säemann, M.D.; Haidinger, M.; Hecking, M.; Hörl, W.H.; Weichhart, T. The multifunctional role of mTOR in innate immunity: implications for transplant immunity. Am. J. Transplant.,  2009, 9(12), 2655-2661.
[http://dx.doi.org/10.1111/j.1600-6143.2009.02832.x ] [PMID:  19788500] 
[182] 
Kang, R.; Tang, D.; Lotze, M.T.; Zeh Iii, H.J. Autophagy is required for IL-2-mediated fibroblast growth. Exp. Cell Res.,  2013, 319(4), 556-565.
[http://dx.doi.org/10.1016/j.yexcr.2012.11.012 ] [PMID:  23195496] 
[183] 
Criollo, A.; Chereau, F.; Malik, S.A.; Niso-Santano, M.; Mariño, G.; Galluzzi, L.; Maiuri, M.C.; Baud, V.; Kroemer, G. Autophagy is required for the activation of NFκB. Cell Cycle,  2012, 11(1), 194-199.
[http://dx.doi.org/10.4161/cc.11.1.18669 ] [PMID:  22186785] 
[184] 
Dickinson, J.D.; Alevy, Y.; Malvin, N.P.; Patel, K.K.; Gunsten, S.P.; Holtzman, M.J.; Stappenbeck, T.S.; Brody, S.L. IL13 activates autophagy to regulate secretion in airway epithelial cells. Autophagy,  2016, 12(2), 397-409.
[http://dx.doi.org/10.1080/15548627.2015.1056967 ] [PMID:  26062017] 
[185] 
Ren, C.; Zhang, X.; Shi, H.; Chen, D.; Duan, Z.; Zhang, H.; Ren, F. Autophagy modulates the levels of inflammatory cytokines in macrophages induced by lipopolysaccharide. Chinese J. Cell. Mol.,  2017, 33(5), 581-585.
[PMID:  28502292] 
[186] 
Ravikumar, B.; Sarkar, S.; Davies, J.E.; Futter, M.; Garcia-Arencibia, M.; Green-Thompson, Z.W.; Jimenez-Sanchez, M.; Korolchuk, V.I.; Lichtenberg, M.; Luo, S.; Massey, D.C.; Menzies, F.M.; Moreau, K.; Narayanan, U.; Renna, M.; Siddiqi, F.H.; Underwood, B.R.; Winslow, A.R.; Rubinsztein, D.C. Regulation of mammalian autophagy in physiology and pathophysiology. Physiol. Rev.,  2010, 90(4), 1383-1435.
[http://dx.doi.org/10.1152/physrev.00030.2009 ] [PMID:  20959619] 
[187] 
Jia, G.; Cheng, G.; Gangahar, D.M.; Agrawal, D.K. Insulin-like growth factor-1 and TNF-alpha regulate autophagy through c-jun N-terminal kinase and Akt pathways in human atherosclerotic vascular smooth cells. Immunol. Cell Biol.,  2006, 84(5), 448-454.
[http://dx.doi.org/10.1111/j.1440-1711.2006.01454.x ] [PMID:  16942488] 
[188] 
Yang, Z.; Klionsky, D.J. Mammalian autophagy: core molecular machinery and signaling regulation. Curr. Opin. Cell Biol.,  2010, 22(2), 124-131.
[http://dx.doi.org/10.1016/j.ceb.2009.11.014 ] [PMID:  20034776] 
[189] 
Jung, C.H.; Ro, S-H.; Cao, J.; Otto, N.M.; Kim, D-H. mTOR regulation of autophagy. FEBS Lett.,  2010, 584(7), 1287-1295.
[http://dx.doi.org/10.1016/j.febslet.2010.01.017 ] [PMID:  20083114] 
[190] 
Cai, S.L.; Tee, A.R.; Short, J.D.; Bergeron, J.M.; Kim, J.; Shen, J.; Guo, R.; Johnson, C.L.; Kiguchi, K.; Walker, C.L. Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning. J. Cell Biol.,  2006, 173(2), 279-289.
[http://dx.doi.org/10.1083/jcb.200507119 ] [PMID:  16636147] 
[191] 
Pierdominici, M.; Vacirca, D.; Delunardo, F.; Ortona, E. mTOR signaling and metabolic regulation of T cells: new potential therapeutic targets in autoimmune diseases. Curr. Pharm. Des.,  2011, 17(35), 3888-3897.
[http://dx.doi.org/10.2174/138161211798357809 ] [PMID:  21933144] 
[192] 
Yang, H.; Wang, X.; Zhang, Y.; Liu, H.; Liao, J.; Shao, K.; Chu, Y.; Liu, G. Modulation of TSC-mTOR signaling on immune cells in immunity and autoimmunity. J. Cell. Physiol.,  2014, 229(1), 17-26.
[PMID:  23804073] 
[193] 
Clark, C.A.; Gupta, H.B.; Curiel, T.J. Tumor cell-intrinsic CD274/PD-L1: A novel metabolic balancing act with clinical potential. Autophagy,  2017, 13(5), 987-988.
[http://dx.doi.org/10.1080/15548627.2017.1280223 ] [PMID:  28368722] 
[194] 
Longhi, M.S.; Liberal, R.; Holder, B.; Robson, S.C.; Ma, Y.; Mieli-Vergani, G.; Vergani, D. Inhibition of interleukin-17 promotes differentiation of CD25- cells into stable t regulatory cells in patients with au-toimmune hepatitis. Gastroenterology,  2012, 142(7), 1526-1535.
[http://dx.doi.org/10.1053/j.gastro.2012.02.041]] 
[195] 
Holla, S.; Kurowska-Stolarska, M.; Bayry, J.; Balaji, K.N. Selective inhibition of IFNG-induced autophagy by Mir155- and Mir31-responsive WNT5A and SHH signaling. Autophagy,  2014, 10(2), 311-330.
[http://dx.doi.org/10.4161/auto.27225 ] [PMID:  24343269] 
[196] 
Seto, S.; Tsujimura, K.; Horii, T.; Koide, Y. Autophagy adaptor protein p62/SQSTM1 and autophagy-related gene Atg5 mediate autophagosome formation in response to Mycobacterium tuberculosis infection in dendritic cells. PLoS One,  2013, 8(12)e86017
[http://dx.doi.org/10.1371/journal.pone.0086017 ] [PMID:  24376899] 
[197] 
Dutta, R.K.; Kathania, M.; Raje, M.; Majumdar, S. IL-6 inhibits IFN-γ induced autophagy in Mycobacterium tuberculosis H37Rv infected macrophages. Int. J. Biochem. Cell Biol.,  2012, 44(6), 942-954.
[http://dx.doi.org/10.1016/j.biocel.2012.02.021 ] [PMID:  22426116] 
[198] 
Harris, J.; De Haro, S.A.; Master, S.S.; Keane, J.; Roberts, E.A.; Delgado, M.; Deretic, V. T helper 2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis. Immunity,  2007, 27(3), 505-517.
[http://dx.doi.org/10.1016/j.immuni.2007.07.022 ] [PMID:  17892853] 
[199] 
Wang, Z.; Jia, G.; Li, Y.; Liu, J.; Luo, J.; Zhang, J.; Xu, G.; Chen, G. Clinicopathological signature of p21-activated kinase 1 in prostate cancer and its regulation of proliferation and autophagy via the mTOR signaling pathway. Oncotarget,  2017, 8(14), 22563-22580.
[http://dx.doi.org/10.18632/oncotarget.15124 ] [PMID:  28186966] 
[200] 
Wang, G.; Song, Y.; Liu, T.; Wang, C.; Zhang, Q.; Liu, F.; Cai, X.; Miao, Z.; Xu, H.; Xu, H.; Cao, L.; Li, F. PAK1-mediated MORC2 phosphorylation promotes gastric tumorigenesis. Oncotarget,  2015, 6(12), 9877-9886.
[http://dx.doi.org/10.18632/oncotarget.3185 ] [PMID:  25888627] 
[201] 
Ramachandran, A.; Jaeschke, H. PGAM5: a new player in immune-mediated liver injury. Gut,  2017, 66(4), 567-568.
[http://dx.doi.org/10.1136/gutjnl-2016-312775 ] [PMID:  27797941] 
[202] 
Expression of the serine/threonine kinase hSGK1 in
chronic viral hepatitis. Cell. Physiol. Biochem., 2002,
12(1), 47-54.. 
[http://dx.doi.org/10.1159/000047826] [PMID: 11914548] 
Rights & Permissions Print Cite
Article Metrics
29
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/0929867326666190402120231	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
当代药物化学

自身免疫性肝炎和星状细胞:对自噬作用的认识

摘要

当代药物化学

自身免疫性肝炎和星状细胞:对自噬作用的认识

摘要 Play Pause

Related Journals

Related Books

Related Articles

摘要
