Login Register Cart 0
Generic placeholder image

Current Drug Targets

Editor-in-Chief

ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Targeting Hepatic Stellate Cell Death to Reverse Hepatic Fibrosis

Author(s): Xiangting Zhang, Yuan Zeng, Luying Zhao, Qian Xu, Dan Miao and Fujun Yu*

Volume 24, Issue 7, 2023

Published on: 23 May, 2023

Page: [568 - 583] Pages: 16

DOI: 10.2174/1389450124666230330135834

Price: $65

conference banner
Abstract

To date, the incidence and mortality of chronic liver diseases such as cirrhosis and hepatocellular carcinoma due to the continued progression of hepatic fibrosis are increasing annually. Unfortunately, although a large number of studies have exhibited that some drugs have great potential for anti-fibrosis in animal and clinical trials, no specific anti-fibrosis drugs have been developed, and there is no better treatment for advanced cirrhosis than liver transplantation. It is a prevailing viewpoint that hepatic stellate cells (HSCs), as the mainstay of extracellular matrix secretion, are of great concern in the development of hepatic fibrosis. Therefore, targeting HSCs becomes extremely important to confront hepatic fibrosis. As previous studies described, inhibition of HSC activation and proliferation, induction of HSC death, and restoration of HSC quiescence are effective in reversing hepatic fibrosis. This review focuses on the current status of research on the treatment of hepatic fibrosis by inducing HSC death and elucidates the HSC death modes in detail and the crosstalk between them.

« Previous Next »
Graphical Abstract

[1]
Bertheloot D, Latz E, Franklin BS. Necroptosis, pyroptosis and apoptosis: An intricate game of cell death. Cell Mol Immunol 2021; 18(5): 1106-21.
[http://dx.doi.org/10.1038/s41423-020-00630-3] [PMID: 33785842]
[2]
Wu J, Zern MA. Hepatic stellate cells: A target for the treatment of liver fibrosis. J Gastroenterol 2000; 35(9): 665-72.
[http://dx.doi.org/10.1007/s005350070045] [PMID: 11023037]
[3]
Iredale JP. Cirrhosis: New research provides a basis for rational and targeted treatments. BMJ 2003; 327(7407): 143-7.
[http://dx.doi.org/10.1136/bmj.327.7407.143] [PMID: 12869458]
[4]
Wang J, Chu ESH, Chen HY, et al. MicroRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway. Oncotarget 2015; 6(9): 7325-38.
[http://dx.doi.org/10.18632/oncotarget.2621] [PMID: 25356754]
[5]
Albanis E, Friedman SL. Antifibrotic agents for liver disease. Am J Transplant 2006; 6(1): 12-9.
[http://dx.doi.org/10.1111/j.1600-6143.2005.01143.x] [PMID: 16433751]
[6]
Liang J, Yuan H, Xu L, et al. Study on the effect of Mongolian medicine Qiwei Qinggan powder on hepatic fibrosis through JAK2/STAT3 pathway. Biosci Biotechnol Biochem 2021; 85(4): 775-85.
[http://dx.doi.org/10.1093/bbb/zbab001] [PMID: 33686395]
[7]
Iredale JP. Models of liver fibrosis: Exploring the dynamic nature of inflammation and repair in a solid organ. J Clin Invest 2007; 117(3): 539-48.
[http://dx.doi.org/10.1172/JCI30542] [PMID: 17332881]
[8]
Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. J Hepatol 2019; 70(1): 151-71.
[http://dx.doi.org/10.1016/j.jhep.2018.09.014] [PMID: 30266282]
[9]
Bi S, Chu F, Wang M, et al. Ligustrazine-oleanolic acid glycine derivative, G-TOA, selectively inhibited the proliferation and induced apoptosis of activated HSC-T6 cells. Molecules 2016; 21(11): 1599.
[http://dx.doi.org/10.3390/molecules21111599] [PMID: 27886086]
[10]
Shang L, Hosseini M, Liu X, Kisseleva T, Brenner DA. Human hepatic stellate cell isolation and characterization. J Gastroenterol 2018; 53(1): 6-17.
[http://dx.doi.org/10.1007/s00535-017-1404-4] [PMID: 29094206]
[11]
Friedman SL. Hepatic stellate cells: Protean, multifunctional, and enigmatic cells of the liver. Physiol Rev 2008; 88(1): 125-72.
[http://dx.doi.org/10.1152/physrev.00013.2007] [PMID: 18195085]
[12]
Dooley S, Delvoux B, Lahme B, Mangasser-Stephan K, Gressner AM. Modulation of transforming growth factorβ response and signaling during transdifferentiation of rat hepatic stellate cells to myofibroblasts. Hepatology 2000; 31(5): 1094-106.
[http://dx.doi.org/10.1053/he.2000.6126] [PMID: 10796885]
[13]
Iredale JP. Hepatic stellate cell behavior during resolution of liver injury. Semin Liver Dis 2001; 21(3): 427-36.
[http://dx.doi.org/10.1055/s-2001-17557] [PMID: 11586470]
[14]
Benyon RC, Arthur MJP. Extracellular matrix degradation and the role of hepatic stellate cells. Semin Liver Dis 2001; 21(3): 373-84.
[http://dx.doi.org/10.1055/s-2001-17552] [PMID: 11586466]
[15]
Friedman SL, Bansal MB. Reversal of hepatic fibrosis-fact or fantasy? Hepatology 2006; 43(S1) (Suppl. 1): S82-8.
[http://dx.doi.org/10.1002/hep.20974] [PMID: 16447275]
[16]
Yan Y, Zeng J, Xing L, Li C. Extra- and intra-cellular mechanisms of hepatic stellate cell activation. Biomedicines 2021; 9(8): 1014.
[http://dx.doi.org/10.3390/biomedicines9081014] [PMID: 34440218]
[17]
Higashi T, Friedman SL, 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]
[18]
Nirmala JG, Lopus M. Cell death mechanisms in eukaryotes. Cell Biol Toxicol 2020; 36(2): 145-64.
[http://dx.doi.org/10.1007/s10565-019-09496-2] [PMID: 31820165]
[19]
Tsvetkov P, Coy S, Petrova B, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science 2022; 375(6586): 1254-61.
[http://dx.doi.org/10.1126/science.abf0529] [PMID: 35298263]
[20]
Mehal W, Imaeda A. Cell death and fibrogenesis. Semin Liver Dis 2010; 30(3): 226-31.
[http://dx.doi.org/10.1055/s-0030-1255352] [PMID: 20665375]
[21]
Kerr J F R, Wyllie AH, Currie AR. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972; 26(4): 239-57.
[http://dx.doi.org/10.1038/bjc.1972.33] [PMID: 4561027]
[22]
Kist M, Vucic D. Cell death pathways: Intricate connections and disease implications. EMBO J 2021; 40(5): e106700.
[http://dx.doi.org/10.15252/embj.2020106700] [PMID: 33439509]
[23]
Abbas R, Larisch S. Killing by degradation: regulation of apoptosis by the ubiquitin-proteasome-system. Cells 2021; 10(12): 3465.
[http://dx.doi.org/10.3390/cells10123465] [PMID: 34943974]
[24]
Kantari C, Walczak H. Caspase-8 and Bid: Caught in the act between death receptors and mitochondria. Biochim Biophys Acta Mol Cell Res 2011; 1813(4): 558-63.
[http://dx.doi.org/10.1016/j.bbamcr.2011.01.026] [PMID: 21295084]
[25]
He L, Hou X, Fan F, Wu H. Quercetin stimulates mitochondrial apoptosis dependent on activation of endoplasmic reticulum stress in hepatic stellate cells. Pharm Biol 2016; 54(12): 3237-43.
[http://dx.doi.org/10.1080/13880209.2016.1223143] [PMID: 27572285]
[26]
Di Sario A, Bendia E, Svegliati Baroni G, et al. Effect of pirfenidone on rat hepatic stellate cell proliferation and collagen production. J Hepatol 2002; 37(5): 584-91.
[http://dx.doi.org/10.1016/S0168-8278(02)00245-3] [PMID: 12399223]
[27]
Cory S, Huang DCS, Adams JM. The Bcl-2 family: Roles in cell survival and oncogenesis. Oncogene 2003; 22(53): 8590-607.
[http://dx.doi.org/10.1038/sj.onc.1207102] [PMID: 14634621]
[28]
Wu L, Mao C, Ming X. Modulation of Bcl-x alternative splicing induces apoptosis of human hepatic stellate cells. BioMed Res Int 2016; 2016: 1-7.
[http://dx.doi.org/10.1155/2016/7478650] [PMID: 27579319]
[29]
Hinz B, Lagares D. Evasion of apoptosis by myofibroblasts: A hallmark of fibrotic diseases. Nat Rev Rheumatol 2020; 16(1): 11-31.
[http://dx.doi.org/10.1038/s41584-019-0324-5] [PMID: 31792399]
[30]
Kim HE, Du F, Fang M, Wang X. Formation of apoptosome is initiated by cytochrome c-induced dATP hydrolysis and subsequent nucleotide exchange on Apaf-1. Proc Natl Acad Sci USA 2005; 102(49): 17545-50.
[http://dx.doi.org/10.1073/pnas.0507900102] [PMID: 16251271]
[31]
Li P, Nijhawan D, Budihardjo I, et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997; 91(4): 479-89.
[http://dx.doi.org/10.1016/S0092-8674(00)80434-1] [PMID: 9390557]
[32]
Kale J, Osterlund EJ, Andrews DW. BCL-2 family proteins: Changing partners in the dance towards death. Cell Death Differ 2018; 25(1): 65-80.
[http://dx.doi.org/10.1038/cdd.2017.186] [PMID: 29149100]
[33]
Vousden KH, Prives C. Blinded by the light: The growing complexity of p53. Cell 2009; 137(3): 413-31.
[http://dx.doi.org/10.1016/j.cell.2009.04.037] [PMID: 19410540]
[34]
Uwagawa T, Yanaga K. Effect of NF-κB inhibition on chemoresistance in biliary–pancreatic cancer. Surg Today 2015; 45(12): 1481-8.
[http://dx.doi.org/10.1007/s00595-015-1129-z] [PMID: 25673034]
[35]
Kucharczak J, Simmons MJ, Fan Y, Gélinas C. To be, or not to be: NF-κB is the answer-role of Rel/NF-κB in the regulation of apoptosis. Oncogene 2003; 22(56): 8961-82.
[http://dx.doi.org/10.1038/sj.onc.1207230] [PMID: 14663476]
[36]
Cheng CF, Pan TM. Ankaflavin and monascin induce apoptosis in activated hepatic stellate cells through suppression of the Akt/NF-κB/p38 signaling pathway. J Agric Food Chem 2016; 64(49): 9326-34.
[http://dx.doi.org/10.1021/acs.jafc.6b03700] [PMID: 27960292]
[37]
Yang H, Chen B, Zhao Z, et al. Heme oxygenase-1 exerts pro-apoptotic effects on hepatic stellate cells in�vitro through regulation of nuclear factor-κB. Exp Ther Med 2018; 16(1): 291-9.
[http://dx.doi.org/10.3892/etm.2018.6185] [PMID: 29896252]
[38]
Ping J, Gao A, Qin H, et al. Indole-3-carbinol enhances the resolution of rat liver fibrosis and stimulates hepatic stellate cell apoptosis by blocking the inhibitor of κB kinase α/inhibitor of κB-α/nuclear factor-κB pathway. J Pharmacol Exp Ther 2011; 339(2): 694-703.
[http://dx.doi.org/10.1124/jpet.111.179820] [PMID: 21862660]
[39]
Oakley F, Trim N, Constandinou CM, et al. Hepatocytes express nerve growth factor during liver injury: Evidence for paracrine regulation of hepatic stellate cell apoptosis. Am J Pathol 2003; 163(5): 1849-58.
[http://dx.doi.org/10.1016/S0002-9440(10)63544-4] [PMID: 14578185]
[40]
Zheng H, Wang X, Zhang Y, Chen L, Hua L, Xu W. Pien-Tze-Huang ameliorates hepatic fibrosis via suppressing NF-κB pathway and promoting HSC apoptosis. J Ethnopharmacol 2019; 244: 111856.
[http://dx.doi.org/10.1016/j.jep.2019.111856]
[41]
Battle T, Frank D. The role of STATs in apoptosis. Curr Mol Med 2002; 2(4): 381-92.
[http://dx.doi.org/10.2174/1566524023362456] [PMID: 12108949]
[42]
Zhao X, Zhang E, Ren X, et al. Edaravone alleviates cell apoptosis and mitochondrial injury in ischemia-reperfusion-induced kidney injury via the JAK/STAT pathway. Biol Res 2020; 53(1): 28.
[http://dx.doi.org/10.1186/s40659-020-00297-0] [PMID: 32620154]
[43]
Wu XX, Wu LM, Fan JJ, et al. Cortex dictamni extract induces apoptosis of activated hepatic stellate cells via STAT1 and attenuates liver fibrosis in mice. J Ethnopharmacol 2011; 135(1): 173-8.
[http://dx.doi.org/10.1016/j.jep.2011.03.010] [PMID: 21396998]
[44]
Martí-Rodrigo A, Alegre F, Moragrega ÁB, et al. Rilpivirine attenuates liver fibrosis through selective STAT1-mediated apoptosis in hepatic stellate cells. Gut 2020; 69(5): 920-32.
[http://dx.doi.org/10.1136/gutjnl-2019-318372] [PMID: 31530714]
[45]
Scheid MP, Woodgett JR. PKB/AKT: Functional insights from genetic models. Nat Rev Mol Cell Biol 2001; 2(10): 760-8.
[http://dx.doi.org/10.1038/35096067] [PMID: 11584303]
[46]
Lee SW, Kim SM, Hur W, et al. Tenofovir disoproxil fumarate directly ameliorates liver fibrosis by inducing hepatic stellate cell apoptosis via downregulation of PI3K/Akt/mTOR signaling pathway. PLoS One 2021; 16(12): e0261067.
[http://dx.doi.org/10.1371/journal.pone.0261067] [PMID: 34879114]
[47]
Zhu H, Shan Y, Ge K, Lu J, Kong W, Jia C. Specific overexpression of Mitofusin-2 in hepatic stellate cells ameliorates liver fibrosis in mice model. Hum Gene Ther 2020; 31(1-2): 103-9.
[http://dx.doi.org/10.1089/hum.2019.153] [PMID: 31802713]
[48]
Zhang Z, Wen H, Weng J, et al. Silencing of EPCAM suppresses hepatic fibrosis and hepatic stellate cell proliferation in mice with alcoholic hepatitis via the PI3K/Akt/mTOR signaling pathway. Cell Cycle 2019; 18(18): 2239-54.
[http://dx.doi.org/10.1080/15384101.2019.1642067] [PMID: 31378124]
[49]
Zhu S, Wang T, Luo F, et al. Astaxanthin inhibits proliferation and induces apoptosis of LX-2 cells by regulating the miR-29b/Bcl-2 pathway. Mol Med Rep 2019; 19(5): 3537-47.
[http://dx.doi.org/10.3892/mmr.2019.10025] [PMID: 30896849]
[50]
Widmann C, Gibson S, Jarpe MB, Johnson GL. Mitogen-activated protein kinase: Conservation of a three-kinase module from yeast to human. Physiol Rev 1999; 79(1): 143-80.
[http://dx.doi.org/10.1152/physrev.1999.79.1.143] [PMID: 9922370]
[51]
Braicu C, Buse M, Busuioc C, et al. A comprehensive review on MAPK: A promising therapeutic target in cancer. Cancers 2019; 11(10): 1618.
[http://dx.doi.org/10.3390/cancers11101618] [PMID: 31652660]
[52]
Yue J, López JM. Understanding MAPK signaling pathways in apoptosis. Int J Mol Sci 2020; 21(7): 2346.
[http://dx.doi.org/10.3390/ijms21072346] [PMID: 32231094]
[53]
Crosas-Molist E, Fabregat I. Role of NADPH oxidases in the redox biology of liver fibrosis. Redox Biol 2015; 6: 106-11.
[http://dx.doi.org/10.1016/j.redox.2015.07.005] [PMID: 26204504]
[54]
Dunning S, ur Rehman A, Tiebosch MH, et al. Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death. Biochim Biophys Acta Mol Basis Dis 2013; 1832(12): 2027-34.
[http://dx.doi.org/10.1016/j.bbadis.2013.07.008] [PMID: 23871839]
[55]
Kuo LM, Chen PJ, Sung PJ, et al. The bioactive extract of Pinnigorgia sp. induces apoptosis of hepatic stellate cells via ROS-ERK/JNK-caspase-3 signaling. Mar Drugs 2018; 16(1): 19.
[http://dx.doi.org/10.3390/md16010019] [PMID: 29315209]
[56]
Balmanno K, Cook SJ. Tumour cell survival signalling by the ERK1/2 pathway. Cell Death Differ 2009; 16(3): 368-77.
[http://dx.doi.org/10.1038/cdd.2008.148] [PMID: 18846109]
[57]
Saxena NK, Titus MA, Ding X, et al. Leptin as a novel profibrogenic cytokine in hepatic stellate cells: Mitogenesis and inhibition of apoptosis mediated by extracellular regulated kinase (Erk) and Akt phosphorylation. FASEB J 2004; 18(13): 1612-4.
[http://dx.doi.org/10.1096/fj.04-1847fje] [PMID: 15319373]
[58]
Zhang F, Kong DS, Zhang ZL, et al. Tetramethylpyrazine induces G0/G1 cell cycle arrest and stimulates mitochondrial-mediated and caspase-dependent apoptosis through modulating ERK/p53 signaling in hepatic stellate cells in vitro. Apoptosis 2013; 18(2): 135-49.
[http://dx.doi.org/10.1007/s10495-012-0791-5] [PMID: 23247439]
[59]
Wu TH, Wang PW, Lin TY, et al. Antioxidant properties of red raspberry extract alleviate hepatic fibrosis via inducing apoptosis and transdifferentiation of activated hepatic stellate cells. Biomed Pharmacother 2021; 144: 112284.
[http://dx.doi.org/10.1016/j.biopha.2021.112284] [PMID: 34626932]
[60]
Schulze-Osthoff K, Ferrari D, Los M, Wesselborg S, Peter ME. Apoptosis signaling by death receptors. Eur J Biochem 1998; 254(3): 439-59.
[http://dx.doi.org/10.1046/j.1432-1327.1998.2540439.x] [PMID: 9688254]
[61]
Galluzzi L, López-Soto A, Kumar S, Kroemer G. Caspases connect cell-death signaling to organismal homeostasis. Immunity 2016; 44(2): 221-31.
[http://dx.doi.org/10.1016/j.immuni.2016.01.020] [PMID: 26885855]
[62]
Wang X, Wang Y, Zhang J, Kim HP, Ryter SW, Choi AMK. FLIP protects against hypoxia/reoxygenation-induced endothelial cell apoptosis by inhibiting Bax activation. Mol Cell Biol 2005; 25(11): 4742-51.
[http://dx.doi.org/10.1128/MCB.25.11.4742-4751.2005] [PMID: 15899875]
[63]
Lee P, Woo S, Jee JG, Sung S, Kim H. Bisdemethoxycurcumin Induces apoptosis in activated hepatic stellate cells via cannabinoid receptor 2. Molecules 2015; 20(1): 1277-92.
[http://dx.doi.org/10.3390/molecules20011277] [PMID: 25594342]
[64]
Li B, Cong M, Zhu Y, et al. Indole-3-Carbinol induces apoptosis of hepatic stellate cells through K63 De-Ubiquitination of RIP1 in rats. Cell Physiol Biochem 2017; 41(4): 1481-90.
[http://dx.doi.org/10.1159/000470650] [PMID: 28395284]
[65]
Haas TL, Emmerich CH, Gerlach B, et al. Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. Mol Cell 2009; 36(5): 831-44.
[http://dx.doi.org/10.1016/j.molcel.2009.10.013] [PMID: 20005846]
[66]
Wang Y, Kanneganti TD. From pyroptosis, apoptosis and necroptosis to PANoptosis: A mechanistic compendium of programmed cell death pathways. Comput Struct Biotechnol J 2021; 19: 4641-57.
[http://dx.doi.org/10.1016/j.csbj.2021.07.038] [PMID: 34504660]
[67]
Wang JS, Wu D, Huang DY, Lin WW. TAK1 inhibition-induced RIP1-dependent apoptosis in murine macrophages relies on constitutive TNF-α signaling and ROS production. J Biomed Sci 2015; 22(1): 76.
[http://dx.doi.org/10.1186/s12929-015-0182-7] [PMID: 26381601]
[68]
Ogawa T, Kawada N, Ikeda K. Effect of natural interferon α on proliferation and apoptosis of hepatic stellate cells. Hepatol Int 2009; 3(3): 497-503.
[http://dx.doi.org/10.1007/s12072-009-9129-y] [PMID: 19669254]
[69]
Yang JA, Kong WH, Sung DK, et al. Hyaluronic acid-tumor necrosis factor-related apoptosis-inducing ligand conjugate for targeted treatment of liver fibrosis. Acta Biomater 2015; 12: 174-82.
[http://dx.doi.org/10.1016/j.actbio.2014.10.002] [PMID: 25305513]
[70]
Wang J, Xu F, Zhu D, et al. Schistosoma japonicum soluble egg antigens facilitate hepatic stellate cell apoptosis by downregulating Akt expression and upregulating p53 and DR5 expression. PLoS Negl Trop Dis 2014; 8(8): e3106.
[http://dx.doi.org/10.1371/journal.pntd.0003106] [PMID: 25144704]
[71]
Wang C, Qi R, Li N, et al. Notch1 signaling sensitizes tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human hepatocellular carcinoma cells by inhibiting Akt/Hdm2-mediated p53 degradation and up-regulating p53-dependent DR5 expression. J Biol Chem 2009; 284(24): 16183-90.
[http://dx.doi.org/10.1074/jbc.M109.002105] [PMID: 19376776]
[72]
Ma PF, Gao CC, Yi J, et al. Cytotherapy with M1-polarized macrophages ameliorates liver fibrosis by modulating immune microenvironment in mice. J Hepatol 2017; 67(4): 770-9.
[http://dx.doi.org/10.1016/j.jhep.2017.05.022] [PMID: 28596109]
[73]
Tang X, Yang J, Li J. Accelerative effect of leflunomide on recovery from hepatic fibrosis involves TRAIL-mediated hepatic stellate cell apoptosis. Life Sci 2009; 84(15-16): 552-7.
[http://dx.doi.org/10.1016/j.lfs.2009.01.017] [PMID: 19385008]
[74]
Rasheva VI, Domingos PM. Cellular responses to endoplasmic reticulum stress and apoptosis. Apoptosis 2009; 14(8): 996-1007.
[http://dx.doi.org/10.1007/s10495-009-0341-y] [PMID: 19360473]
[75]
Di Conza G, Ho PC. ER stress responses: An emerging modulator for innate immunity. Cells 2020; 9(3): 695.
[http://dx.doi.org/10.3390/cells9030695] [PMID: 32178254]
[76]
Borkham-Kamphorst E, Steffen BT, Van de Leur E, et al. CCN1/CYR61 overexpression in hepatic stellate cells induces ER stress-related apoptosis. Cell Signal 2016; 28(1): 34-42.
[http://dx.doi.org/10.1016/j.cellsig.2015.10.013] [PMID: 26515130]
[77]
Walter P, Ron D. The unfolded protein response: From stress pathway to homeostatic regulation. Science 2011; 334(6059): 1081-6.
[http://dx.doi.org/10.1126/science.1209038] [PMID: 22116877]
[78]
Bravo R, Parra V, Gatica D, et al. Endoplasmic reticulum and the unfolded protein response: Dynamics and metabolic integration. Int Rev Cell Mol Biol 2013; 301: 215-90.
[http://dx.doi.org/10.1016/B978-0-12-407704-1.00005-1] [PMID: 23317820]
[79]
Momoi T. Caspases involved in ER stress-mediated cell death. J Chem Neuroanat 2004; 28(1-2): 101-5.
[http://dx.doi.org/10.1016/j.jchemneu.2004.05.008] [PMID: 15363495]
[80]
Liu H, Dai L, Wang M, Feng F, Xiao Y. Tunicamycin induces hepatic stellate cell apoptosis through calpain-2/Ca2 +-dependent endoplasmic reticulum stress pathway. Front Cell Dev Biol 2021; 9: 684857.
[http://dx.doi.org/10.3389/fcell.2021.684857] [PMID: 34604209]
[81]
Ma Y, Li Y, Zhang H, Wang Y, Wu C, Huang W. Malvidin induces hepatic stellate cell apoptosis via the endoplasmic reticulum stress pathway and mitochondrial pathway. Food Sci Nutr 2020; 8(9): 5095-106.
[http://dx.doi.org/10.1002/fsn3.1810] [PMID: 32994970]
[82]
Bian M, He J, Jin H, et al. Oroxylin A induces apoptosis of activated hepatic stellate cells through endoplasmic reticulum stress. Apoptosis 2019; 24(11-12): 905-20.
[http://dx.doi.org/10.1007/s10495-019-01568-2] [PMID: 31538267]
[83]
Wu JS, Chiu V, Lan CC, et al. Chrysophanol prevents lipopolysaccharide-induced hepatic stellate cell activation by upregulating apoptosis, oxidative stress, and the unfolded protein response. Evid Based Complement Alternat Med 2020; 2020: 1-11.
[http://dx.doi.org/10.1155/2020/8426051] [PMID: 32714424]
[84]
Langer DA, Das A, Semela D, et al. Nitric oxide promotes caspase-independent hepatic stellate cell apoptosis through the generation of reactive oxygen species. Hepatology 2008; 47(6): 1983-93.
[http://dx.doi.org/10.1002/hep.22285] [PMID: 18459124]
[85]
Mòdol T, Natal C, Pérez de Obanos MP, Domingo de Miguel E, Iraburu MJ, López-Zabalza MJ. Apoptosis of hepatic stellate cells mediated by specific protein nitration. Biochem Pharmacol 2011; 81(3): 451-8.
[http://dx.doi.org/10.1016/j.bcp.2010.10.017] [PMID: 21056031]
[86]
Dong Z, Su L, Esmaili S, et al. Adiponectin attenuates liver fibrosis by inducing nitric oxide production of hepatic stellate cells. J Mol Med 2015; 93(12): 1327-39.
[http://dx.doi.org/10.1007/s00109-015-1313-z] [PMID: 26153548]
[87]
Mòdol T, Brice N, Ruiz de Galarreta M, et al. Fibronectin peptides as potential regulators of hepatic fibrosis through apoptosis of hepatic stellate cells. J Cell Physiol 2015; 230(3): 546-53.
[http://dx.doi.org/10.1002/jcp.24714] [PMID: 24976518]
[88]
Chakraborty JB, Oakley F, Walsh MJ. Mechanisms and biomarkers of apoptosis in liver disease and fibrosis. Int J Hepatol 2012; 2012: 1-10.
[http://dx.doi.org/10.1155/2012/648915] [PMID: 22567408]
[89]
Ahsan MK, Mehal WZ. Activation of adenosine receptor A2A increases HSC proliferation and inhibits death and senescence by down-regulation of p53 and Rb. Front Pharmacol 2014; 5: 69.
[http://dx.doi.org/10.3389/fphar.2014.00069] [PMID: 24782773]
[90]
Zhang M, Serna-Salas S, Damba T, Borghesan M, Demaria M, Moshage H. Hepatic stellate cell senescence in liver fibrosis: Characteristics, mechanisms and perspectives. Mech Ageing Dev 2021; 199: 111572.
[http://dx.doi.org/10.1016/j.mad.2021.111572] [PMID: 34536446]
[91]
Abriss B, Hollweg G, Gressner AM, Weiskirchen R. Adenoviralmediated transfer of p53 or retinoblastoma protein blocks cell proliferation and induces apoptosis in culture-activated hepatic stellate cells. J Hepatol 2003; 38(2): 169-78.
[http://dx.doi.org/10.1016/S0168-8278(02)00361-6] [PMID: 12547405]
[92]
Campisi J, d’Adda di Fagagna F. Cellular senescence: When bad things happen to good cells. Nat Rev Mol Cell Biol 2007; 8(9): 729-40.
[http://dx.doi.org/10.1038/nrm2233] [PMID: 17667954]
[93]
Krizhanovsky V, Yon M, Dickins RA, et al. Senescence of activated stellate cells limits liver fibrosis. Cell 2008; 134(4): 657-67.
[http://dx.doi.org/10.1016/j.cell.2008.06.049] [PMID: 18724938]
[94]
Loo TM, Kamachi F, Watanabe Y, et al. Gut microbiota promotes obesity-associated liver cancer through PGE2-mediated suppression of antitumor immunity. Cancer Discov 2017; 7(5): 522-38.
[http://dx.doi.org/10.1158/2159-8290.CD-16-0932] [PMID: 28202625]
[95]
Muñoz-Espín D, Serrano M. Cellular senescence: From physiology to pathology. Nat Rev Mol Cell Biol 2014; 15(7): 482-96.
[http://dx.doi.org/10.1038/nrm3823] [PMID: 24954210]
[96]
Thuy LTT, Van Thuy TT, Matsumoto Y, et al. Absence of cytoglobin promotes multiple organ abnormalities in aged mice. Sci Rep 2016; 6(1): 24990.
[http://dx.doi.org/10.1038/srep24990] [PMID: 27146058]
[97]
Serna-Salas SA, Arroyave-Ospina JC, Zhang M, et al. α-1 Adrenergic receptor antagonist doxazosin reverses hepatic stellate cells activation via induction of senescence. Mech Ageing Dev 2022; 201: 111617.
[http://dx.doi.org/10.1016/j.mad.2021.111617] [PMID: 34958827]
[98]
Laberge RM, Awad P, Campisi J, Desprez PY. Epithelial-mesenchymal transition induced by senescent fibroblasts. Cancer Microenviron 2012; 5(1): 39-44.
[http://dx.doi.org/10.1007/s12307-011-0069-4] [PMID: 21706180]
[99]
Kojima H, Inoue T, Kunimoto H, Nakajima K. IL-6-STAT3 signaling and premature senescence. JAK-STAT 2013; 2(4): e25763.
[http://dx.doi.org/10.4161/jkst.25763] [PMID: 24416650]
[100]
Kong X, Feng D, Wang H, et al. Interleukin-22 induces hepatic stellate cell senescence and restricts liver fibrosis in mice. Hepatology 2012; 56(3): 1150-9.
[http://dx.doi.org/10.1002/hep.25744] [PMID: 22473749]
[101]
Chen J, Xu T, Zhu D, et al. Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21 pathway. Cell Death Dis 2016; 7(7): e2315-5.
[http://dx.doi.org/10.1038/cddis.2016.228] [PMID: 27468691]
[102]
Lao Y, Li Y, Zhang P, et al. Targeting endothelial Erk1/2-Akt axis as a regeneration strategy to bypass fibrosis during chronic liver injury in mice. Mol Ther 2018; 26(12): 2779-97.
[http://dx.doi.org/10.1016/j.ymthe.2018.08.016] [PMID: 30266653]
[103]
Luo J, Li L, Chang B, et al. Mannan-binding lectin via interaction with cell surface calreticulin promotes senes-cence of activated hepatic stellate cells to limit liver fibrosis progression. Cell Mol Gastroenterol Hepatol 2022; 14(1): 75-99.
[http://dx.doi.org/10.1016/j.jcmgh.2022.03.011] [PMID: 35381393]
[104]
Yang J, Lu Y, Yang P, et al. MicroRNA-145 induces the senescence of activated hepatic stellate cells through the activation of p53 pathway by ZEB2. J Cell Physiol 2019; 234(5): 7587-99.
[http://dx.doi.org/10.1002/jcp.27521] [PMID: 30479019]
[105]
Jin H, Lian N, Zhang F, et al. Activation of PPARγ/P53 signaling is required for curcumin to induce hepatic stellate cell senescence. Cell Death Dis 2016; 7(4): e2189-9.
[http://dx.doi.org/10.1038/cddis.2016.92] [PMID: 27077805]
[106]
Wan Y, McDaniel K, Wu N, et al. Regulation of cellular senescence by miR-34a in alcoholic liver injury. Am J Pathol 2017; 187(12): 2788-98.
[http://dx.doi.org/10.1016/j.ajpath.2017.08.027] [PMID: 29128099]
[107]
Xu T, Ding W, Ji X, et al. Molecular mechanisms of ferroptosis and its role in cancer therapy. J Cell Mol Med 2019; 23(8): 4900-12.
[http://dx.doi.org/10.1111/jcmm.14511] [PMID: 31232522]
[108]
Yuan S, Wei C, Liu G, et al. Sorafenib attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis via HIF-1α/SLC7A11 pathway. Cell Prolif 2022; 55(1): e13158.
[http://dx.doi.org/10.1111/cpr.13158] [PMID: 34811833]
[109]
Verbon EH, Trapet PL, Stringlis IA, Kruijs S, Bakker PAHM, Pieterse CMJ. Iron and immunity. Annu Rev Phytopathol 2017; 55(1): 355-75.
[http://dx.doi.org/10.1146/annurev-phyto-080516-035537] [PMID: 28598721]
[110]
Yi J, Wu S, Tan S, et al. Berberine alleviates liver fibrosis through inducing ferrous redox to activate ROS-mediated hepatic stellate cells ferroptosis. Cell Death Discov 2021; 7(1): 374.
[http://dx.doi.org/10.1038/s41420-021-00768-7] [PMID: 34864819]
[111]
Wang L, Zhang Z, Li M, et al. P53-dependent induction of ferroptosis is required for artemether to alleviate carbon tetrachloride-induced liver fibrosis and hepatic stellate cell activation. IUBMB Life 2019; 71(1): 45-56.
[http://dx.doi.org/10.1002/iub.1895] [PMID: 30321484]
[112]
Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell 2012; 149(5): 1060-72.
[http://dx.doi.org/10.1016/j.cell.2012.03.042] [PMID: 22632970]
[113]
Ho CH, Huang JH, Sun MS, Tzeng IS, Hsu YC, Kuo CY. Wild bitter melon extract regulates LPS-induced hepatic stellate cell activation, inflammation, endoplasmic reticulum stress, and ferroptosis. Evid Based Complement Alternat Med 2021; 2021: 1-11.
[http://dx.doi.org/10.1155/2021/6671129] [PMID: 34239589]
[114]
Zhang Z, Guo M, Shen M, et al. The BRD7-P53-SLC25A28 axis regulates ferroptosis in hepatic stellate cells. Redox Biol 2020; 36: 101619.
[http://dx.doi.org/10.1016/j.redox.2020.101619] [PMID: 32863216]
[115]
Hou W, Xie Y, Song X, et al. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy 2016; 12(8): 1425-8.
[http://dx.doi.org/10.1080/15548627.2016.1187366] [PMID: 27245739]
[116]
Zhang Z, Guo M, Li Y, et al. RNA-binding protein ZFP36/TTP protects against ferroptosis by regulating autophagy signaling pathway in hepatic stellate cells. Autophagy 2020; 16(8): 1482-505.
[http://dx.doi.org/10.1080/15548627.2019.1687985] [PMID: 31679460]
[117]
Zhang Z, Yao Z, Wang L, et al. Activation of ferritinophagy is required for the RNA-binding protein ELAVL1/HuR to regulate ferroptosis in hepatic stellate cells. Autophagy 2018; 14(12): 2083-103.
[http://dx.doi.org/10.1080/15548627.2018.1503146] [PMID: 30081711]
[118]
Latunde-Dada GO. Ferroptosis: Role of lipid peroxidation, iron and ferritinophagy. Biochim Biophys Acta, Gen Subj 2017; 1861(8): 1893-900.
[http://dx.doi.org/10.1016/j.bbagen.2017.05.019] [PMID: 28552631]
[119]
Kong Z, Liu R, Cheng Y. Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway. Biomed Pharmacother 2019; 109: 2043-53.
[http://dx.doi.org/10.1016/j.biopha.2018.11.030] [PMID: 30551460]
[120]
Kocaturk NM, Gozuacik D. Crosstalk between mammalian autophagy and the ubiquitin-proteasome system. Front Cell Dev Biol 2018; 6: 128.
[http://dx.doi.org/10.3389/fcell.2018.00128] [PMID: 30333975]
[121]
Hara T, Nakamura K, Matsui M, et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 2006; 441(7095): 885-9.
[http://dx.doi.org/10.1038/nature04724] [PMID: 16625204]
[122]
Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z. Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J 2007; 26(7): 1749-60.
[http://dx.doi.org/10.1038/sj.emboj.7601623] [PMID: 17347651]
[123]
Shen M, Li Y, Wang Y, et al. N6-methyladenosine modification regulates ferroptosis through autophagy signaling pathway in hepatic stellate cells. Redox Biol 2021; 47: 102151.
[http://dx.doi.org/10.1016/j.redox.2021.102151] [PMID: 34607160]
[124]
Shen M, Guo M, Li Y, et al. m6A methylation is required for dihydroartemisinin to alleviate liver fibrosis by inducing ferroptosis in hepatic stellate cells. Free Radic Biol Med 2022; 182: 246-59.
[http://dx.doi.org/10.1016/j.freeradbiomed.2022.02.028] [PMID: 35248719]
[125]
Zhang Q, Qu Y, Zhang Q, et al. Exosomes derived from hepatitis B virus-infected hepatocytes promote liver fibrosis via miR-222/TFRC axis. Cell Biol Toxicol 2022; 1-15.
[http://dx.doi.org/10.1007/s10565-021-09684-z] [PMID: 34978008]
[126]
Li Y, Jin C, Shen M, et al. Iron regulatory protein 2 is required for artemether -mediated anti-hepatic fibrosis through ferroptosis pathway. Free Radic Biol Med 2020; 160: 845-59.
[http://dx.doi.org/10.1016/j.freeradbiomed.2020.09.008] [PMID: 32947011]
[127]
Jorgensen I, Miao EA. Pyroptotic cell death defends against intracellular pathogens. Immunol Rev 2015; 265(1): 130-42.
[http://dx.doi.org/10.1111/imr.12287] [PMID: 25879289]
[128]
Kong DL, Kong FY, Liu XY, et al. Soluble egg antigen of Schistosoma japonicum induces pyroptosis in hepatic stellate cells by modulating ROS production. Parasit Vectors 2019; 12(1): 475.
[http://dx.doi.org/10.1186/s13071-019-3729-8] [PMID: 31610797]
[129]
Burdette BE, Esparza AN, Zhu H, Wang S. Gasdermin D in pyroptosis. Acta Pharm Sin B 2021; 11(9): 2768-82.
[http://dx.doi.org/10.1016/j.apsb.2021.02.006] [PMID: 34589396]
[130]
Sborgi L, Rühl S, Mulvihill E, et al. GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death. EMBO J 2016; 35(16): 1766-78.
[http://dx.doi.org/10.15252/embj.201694696] [PMID: 27418190]
[131]
Vince JE, Silke J. The intersection of cell death and inflammasome activation. Cell Mol Life Sci 2016; 73(11-12): 2349-67.
[http://dx.doi.org/10.1007/s00018-016-2205-2] [PMID: 27066895]
[132]
Schwartz LM. Autophagic cell death during development-ancient and mysterious. Front Cell Dev Biol 2021; 9: 656370.
[http://dx.doi.org/10.3389/fcell.2021.656370] [PMID: 33898457]
[133]
Malhi H, Gores GJ, Lemasters JJ. Apoptosis and necrosis in the liver: A tale of two deaths? Hepatology 2006; 43(S1) (Suppl. 1): S31-44.
[http://dx.doi.org/10.1002/hep.21062] [PMID: 16447272]
[134]
Baines CP, Kaiser RA, Purcell NH, et al. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 2005; 434(7033): 658-62.
[http://dx.doi.org/10.1038/nature03434] [PMID: 15800627]
[135]
Siegmund SV, Uchinami H, Osawa Y, Brenner DA, Schwabe RF. Anandamide induces necrosis in primary hepatic stellate cells. Hepatology 2005; 41(5): 1085-95.
[http://dx.doi.org/10.1002/hep.20667] [PMID: 15841466]
[136]
Yang Q, Liu HY, Zhang YW, Wu WJ, Tang WX. Anandamide induces cell death through lipid rafts in hepatic stellate cells. J Gastroenterol Hepatol 2010; 25(5): 991-1001.
[http://dx.doi.org/10.1111/j.1440-1746.2009.06122.x] [PMID: 20059638]
[137]
Hsieh SC, Wu CH, Wu CC, et al. Gallic acid selectively induces the necrosis of activated hepatic stellate cells via a calcium-dependent calpain I activation pathway. Life Sci 2014; 102(1): 55-64.
[http://dx.doi.org/10.1016/j.lfs.2014.02.041] [PMID: 24631138]
[138]
Denton D, Kumar S. Autophagy-dependent cell death. Cell Death Differ 2019; 26(4): 605-16.
[http://dx.doi.org/10.1038/s41418-018-0252-y] [PMID: 30568239]
[139]
Green DR, Llambi F. Cell death signaling. Cold Spring Harb Perspect Biol 2015; 7(12): a006080.
[http://dx.doi.org/10.1101/cshperspect.a006080] [PMID: 26626938]
[140]
Yu L, Chen Y, Tooze SA. Autophagy pathway: Cellular and molecular mechanisms. Autophagy 2018; 14(2): 207-15.
[http://dx.doi.org/10.1080/15548627.2017.1378838] [PMID: 28933638]
[141]
Denardin CC, Martins LAM, Parisi MM, et al. Autophagy induced by purple pitanga (Eugenia uniflora L.) extract triggered a cooperative effect on inducing the hepatic stellate cell death. Cell Biol Toxicol 2017; 33(2): 197-206.
[http://dx.doi.org/10.1007/s10565-016-9366-5] [PMID: 27744523]
[142]
Galluzzi L, Baehrecke EH, Ballabio A, et al. Molecular definitions of autophagy and related processes. EMBO J 2017; 36(13): 1811-36.
[http://dx.doi.org/10.15252/embj.201796697] [PMID: 28596378]
[143]
Zhang XL, Chen ZN, Huang QF, et al. Methyl helicterate inhibits hepatic stellate cell activation through modulation of apoptosis and autophagy. Cell Physiol Biochem 2018; 51(2): 897-908.
[http://dx.doi.org/10.1159/000495390] [PMID: 30466104]
[144]
Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: Crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 2007; 8(9): 741-52.
[http://dx.doi.org/10.1038/nrm2239] [PMID: 17717517]
[145]
He C, Levine B. The Beclin 1 interactome. Curr Opin Cell Biol 2010; 22(2): 140-9.
[http://dx.doi.org/10.1016/j.ceb.2010.01.001] [PMID: 20097051]
[146]
Hao H, Zhang D, Shi J, et al. Sorafenib induces autophagic cell death and apoptosis in hepatic stellate cell through the JNK and Akt signaling pathways. Anticancer Drugs 2016; 27(3): 192-203.
[http://dx.doi.org/10.1097/CAD.0000000000000316] [PMID: 26629768]
[147]
Codogno P, Mehrpour M, Proikas-Cezanne T. Canonical and non-canonical autophagy: Variations on a common theme of self-eating? Nat Rev Mol Cell Biol 2012; 13(1): 7-12.
[http://dx.doi.org/10.1038/nrm3249] [PMID: 22166994]
[148]
Yu Z, Jv Y, Cai L, et al. Gambogic acid attenuates liver fibrosis by inhibiting the PI3K/AKT and MAPK signaling pathways via inhibiting HSP90. Toxicol Appl Pharmacol 2019; 371: 63-73.
[http://dx.doi.org/10.1016/j.taap.2019.03.028] [PMID: 30953615]
[149]
Li Y, Chen Y, Huang H, et al. Autophagy mediated by endoplasmic reticulum stress enhances the caffeine-induced apoptosis of hepatic stellate cells. Int J Mol Med 2017; 40(5): 1405-14.
[http://dx.doi.org/10.3892/ijmm.2017.3145] [PMID: 28949381]
[150]
Li J, Zhang L, Xia Q, Fu J, Zhou Z, Lin F. Hedgehog signaling inhibitor GANT61 induces endoplasmic reticulum stress-mediated protective autophagy in hepatic stellate cells. Biochem Biophys Res Commun 2017; 493(1): 487-93.
[http://dx.doi.org/10.1016/j.bbrc.2017.08.164] [PMID: 28870808]
[151]
Kang C, Elledge SJ. How autophagy both activates and inhibits cellular senescence. Autophagy 2016; 12(5): 898-9.
[http://dx.doi.org/10.1080/15548627.2015.1121361] [PMID: 27129029]
[152]
Zhang Z, Yao Z, Zhao S, et al. Interaction between autophagy and senescence is required for dihydroartemisinin to alleviate liver fibrosis. Cell Death Dis 2017; 8(6): e2886-6.
[http://dx.doi.org/10.1038/cddis.2017.255] [PMID: 28617435]
[153]
Lee YA, Wallace MC, Friedman SL. Pathobiology of liver fibrosis: A translational success story. Gut 2015; 64(5): 830-41.
[http://dx.doi.org/10.1136/gutjnl-2014-306842] [PMID: 25681399]
[154]
Poilil Surendran S, George Thomas R, Moon MJ, Jeong YY. Nanoparticles for the treatment of liver fibrosis. Int J Nanomedicine 2017; 12: 6997-7006.
[http://dx.doi.org/10.2147/IJN.S145951] [PMID: 29033567]
[155]
Guo Z, Li D, Peng H, et al. Specific hepatic stellate cell-penetrating peptide targeted delivery of a KLA peptide reduces collagen accumulation by inducing apoptosis. J Drug Target 2017; 25(8): 715-23.
[http://dx.doi.org/10.1080/1061186X.2017.1322598] [PMID: 28447897]
[156]
Meng D, Li Z, Wang G, Ling L, Wu Y, Zhang C. Carvedilol attenuates liver fibrosis by suppressing autophagy and promoting apoptosis in hepatic stellate cells. Biomed Pharmacother 2018; 108: 1617-27.
[http://dx.doi.org/10.1016/j.biopha.2018.10.005] [PMID: 30372864]
[157]
Shaker ME, Ghani A, Shiha GE, Ibrahim TM, Mehal WZ. Nilotinib induces apoptosis and autophagic cell death of activated hepatic stellate cells via inhibition of histone deacetylases. Biochim Biophys Acta Mol Cell Res 2013; 1833(8): 1992-2003.
[http://dx.doi.org/10.1016/j.bbamcr.2013.02.033] [PMID: 23499874]
[158]
Li Z, Zhao L, Xia Y, Chen J, Hua M, Sun Y. Schisandrin B attenuates hepatic stellate cell activation and promotes apoptosis to protect against liver fibrosis. Molecules 2021; 26(22): 6882.
[http://dx.doi.org/10.3390/molecules26226882] [PMID: 34833975]
[159]
Du XS, Li HD, Yang XJ, et al. Wogonin attenuates liver fibrosis via regulating hepatic stellate cell activation and apoptosis. Int Immunopharmacol 2019; 75: 105671.
[http://dx.doi.org/10.1016/j.intimp.2019.05.056] [PMID: 31377590]
[160]
Duval F, Moreno-Cuevas JE, González-Garza MT, Rodríguez- Montalvo C, Cruz-Vega DE. Liver fibrosis and protection mechanisms action of medicinal plants targeting apoptosis of hepatocytes and hepatic stellate cells. Adv Pharmacol Sci 2014; 2014: 1-11.
[http://dx.doi.org/10.1155/2014/373295] [PMID: 25505905]
[161]
Lin X, Zhang S, Huang Q, et al. Protective effect of Fufang-Liu-Yue-Qing, a traditional Chinese herbal formula, on CCl4 induced liver fibrosis in rats. J Ethnopharmacol 2012; 142(2): 548-56.
[http://dx.doi.org/10.1016/j.jep.2012.05.040] [PMID: 22658988]
[162]
Chen CH, Chen MF, Huang SJ, et al. Saikosaponin a induces apoptosis through mitochondria-dependent pathway in hepatic stellate cells. Am J Chin Med 2017; 45(2): 351-68.
[http://dx.doi.org/10.1142/S0192415X17500227] [PMID: 28231747]
[163]
Wang Q, Du H, Li M, et al. MAPK signal transduction pathway regulation: A novel mechanism of Rat HSC-T6 Cell apoptosis induced by FUZHENGHUAYU tablet. Evid Based Complement Alternat Med 2013; 2013: 1-13.
[http://dx.doi.org/10.1155/2013/368103] [PMID: 23762126]
[164]
Bai F, Huang Q, Nie J, et al. Trolline ameliorates liver fibrosis by inhibiting the NF-κB pathway, Promoting HSC apoptosis and suppressing autophagy. Cell Physiol Biochem 2017; 44(2): 436-46.
[http://dx.doi.org/10.1159/000485009] [PMID: 29141243]
[165]
Wang Y, Wang R, Wang Y, Peng R, Wu Y, Yuan Y. Ginkgo biloba extract mitigates liver fibrosis and apoptosis by regulating p38 MAPK, NF-κB/IκBα, and Bcl-2/Bax signaling. Drug Des Devel Ther 2015; 9: 6303-17.
[PMID: 26664050]
[166]
Pan TL, Wang PW. Explore the molecular mechanism of apoptosis induced by tanshinone IIA on activated rat hepatic stellate cells. Evid Based Complement Alternat Med 2012; 2012: 1-15.
[http://dx.doi.org/10.1155/2012/734987] [PMID: 23346212]
[167]
Bai T, Lian LH, Wu YL, Wan Y, Nan JX. Thymoquinone attenuates liver fibrosis via PI3K and TLR4 signaling pathways in activated hepatic stellate cells. Int Immunopharmacol 2013; 15(2): 275-81.
[http://dx.doi.org/10.1016/j.intimp.2012.12.020] [PMID: 23318601]
[168]
Duan Y, Li J, Jing X, Ding X, Yu Y, Zhao Q. Fucoidan induces apoptosis and inhibits proliferation of hepatocellular carcinoma via the p38 MAPK/ERK and PI3K/Akt signal pathways. Cancer Manag Res 2020; 12: 1713-23.
[http://dx.doi.org/10.2147/CMAR.S243495] [PMID: 32210612]
[169]
Chen W, Yan X, Yang A, Xu A, Huang T, You H. miRNA-150-5p promotes hepatic stellate cell proliferation and sensitizes hepatocyte apoptosis during liver fibrosis. Epigenomics 2020; 12(1): 53-67.
[http://dx.doi.org/10.2217/epi-2019-0104] [PMID: 31833387]
[170]
Wang Y, Du J, Niu X, et al. MiR-130a-3p attenuates activation and induces apoptosis of hepatic stellate cells in nonalcoholic fibrosing steatohepatitis by directly targeting TGFBR1 and TGFBR2. Cell Death Dis 2017; 8(5): e2792.
[http://dx.doi.org/10.1038/cddis.2017.10] [PMID: 28518142]
[171]
Li H, Zhang L, Cai N, Zhang B, Sun S. MicroRNA-494-3p prevents liver fibrosis and attenuates hepatic stellate cell activation by inhibiting proliferation and inducing apoptosis through targeting TRAF3. Ann Hepatol 2021; 23: 100305.
[http://dx.doi.org/10.1016/j.aohep.2021.100305] [PMID: 33434689]
[172]
Wu X, Zhi F, Lun W, Deng Q, Zhang W. Baicalin inhibits PDGF-BB-induced hepatic stellate cell proliferation, apoptosis, invasion, migration and activation via the miR-3595/ACSL4 axis. Int J Mol Med 2018; 41(4): 1992-2002.
[http://dx.doi.org/10.3892/ijmm.2018.3427] [PMID: 29393361]
[173]
He Y, Huang C, Sun X, Long X, Lv X, Li J. MicroRNA-146a modulates TGF-beta1-induced hepatic stellate cell proliferation by targeting SMAD4. Cell Signal 2012; 24(10): 1923-30.
[http://dx.doi.org/10.1016/j.cellsig.2012.06.003] [PMID: 22735812]
[174]
Guo CJ, Pan Q, Li DG, Sun H, Liu BW. miR-15b and miR-16 are implicated in activation of the rat hepatic stellate cell: An essential role for apoptosis. J Hepatol 2009; 50(4): 766-78.
[http://dx.doi.org/10.1016/j.jhep.2008.11.025] [PMID: 19232449]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy