Activating Protein-1 (AP-1): A Promising Target for the Treatment of
Fibrotic Diseases

Zixin      Pi; Xiangning      Qiu; Jiani      Liu; Yaqian      Shi; Zhuotong      Zeng; Rong      Xiao
doi:10.2174/0929867330666230209100059
Abstract

The fibrosis of tissues and organs occurs via an aberrant tissue remodeling process characterized by an excessive deposition of extracellular matrix, which can lead to organ dysfunction, organ failure, and death. Because the pathogenesis of fibrosis remains unclear and elusive, there is currently no medication to reverse it; hence, this process deserves further study. Activating protein-1 (AP-1)-comprising Jun (c-Jun, JunB, JunD), Fos (c-fos, FosB, Fra1, and Fra2), and activating transcription factor-is a versatile dimeric transcription factor. Numerous studies have demonstrated that AP-1 plays a crucial role in advancing tissue and organ fibrosis via induction of the expression of fibrotic molecules and activating fibroblasts. This review focuses on the role of AP-1 in a range of fibrotic disorders as well as on the antifibrotic effects of AP-1 inhibitors. It also discusses the potential of AP-1 as a new therapeutic target in conditions involving tissue and organ fibrosis.
« Previous Next »
[1]
Shaulian, E.; Karin, M. AP-1 as a regulator of cell life and death. Nat. Cell Biol.,  2002, 4(5), E131-E136.
 [http://dx.doi.org/10.1038/ncb0502-e131] [PMID: 11988758]

[2]
Madrigal, P.; Alasoo, K. AP-1 takes centre stage in enhancer chromatin dynamics. Trends Cell Biol.,  2018, 28(7), 509-511.
 [http://dx.doi.org/10.1016/j.tcb.2018.04.009] [PMID: 29778529]

[3]
Gozdecka, M.; Breitwieser, W. The roles of ATF2 (activating transcription factor 2) in tumorigenesis. Biochem. Soc. Trans.,  2012, 40(1), 230-234.
 [http://dx.doi.org/10.1042/BST20110630] [PMID: 22260696]

[4]
Zenz, R.; Eferl, R.; Scheinecker, C.; Redlich, K.; Smolen, J.; Schonthaler, H.B.; Kenner, L.; Tschachler, E.; Wagner, E.F. Activator protein 1 (Fos/Jun) functions in inflammatory bone and skin disease. Arthritis Res. Ther.,  2007, 10(1), 201.
 [http://dx.doi.org/10.1186/ar2338] [PMID: 18226189]

[5]
Atsaves, V.; Leventaki, V.; Rassidakis, G.Z.; Claret, F.X. AP-1 transcription factors as regulators of immune responses in cancer. Cancers (Basel),  2019, 11(7), 1037.
 [http://dx.doi.org/10.3390/cancers11071037] [PMID: 31340499]

[6]
Wernig, G.; Chen, S.Y.; Cui, L.; Van Neste, C.; Tsai, J.M.; Kambham, N.; Vogel, H.; Natkunam, Y.; Gilliland, D.G.; Nolan, G.; Weissman, I.L. Unifying mechanism for different fibrotic diseases. Proc. Natl. Acad. Sci. USA,  2017, 114(18), 4757-4762.
 [http://dx.doi.org/10.1073/pnas.1621375114] [PMID: 28424250]

[7]
Park, J.; Eisenbarth, D.; Choi, W.; Kim, H.; Choi, C.; Lee, D.; Lim, D.S. YAP and AP-1 cooperate to initiate pancreatic cancer development from ductal cells in mice. Cancer Res.,  2020, 80(21), 4768-4779.
 [http://dx.doi.org/10.1158/0008-5472.CAN-20-0907] [PMID: 32900774]

[8]
Chen, G.L.; Li, R.; Chen, X.X.; Wang, J.; Cao, S.; Song, R.; Zhao, M.C.; Li, L.M.; Hannemmann, N.; Schett, G.; Qian, C.; Bozec, A. Fra-2/AP-1 regulates melanoma cell metastasis by downregulating Fam212b. Cell Death Differ.,  2021, 28(4), 1364-1378.
 [http://dx.doi.org/10.1038/s41418-020-00660-4] [PMID: 33188281]

[9]
Henderson, N.C.; Rieder, F.; Wynn, T.A. Fibrosis: From mechanisms to medicines. Nature,  2020, 587(7835), 555-566.
 [http://dx.doi.org/10.1038/s41586-020-2938-9] [PMID: 33239795]

[10]
Zhao, X.; Kwan, J.Y.Y.; Yip, K.; Liu, P.P.; Liu, F.F. Targeting metabolic dysregulation for fibrosis therapy. Nat. Rev. Drug Discov.,  2020, 19(1), 57-75.
 [http://dx.doi.org/10.1038/s41573-019-0040-5] [PMID: 31548636]

[11]
Korman, B. Evolving insights into the cellular and molecular pathogenesis of fibrosis in systemic sclerosis. Transl. Res.,  2019, 209, 77-89.
 [http://dx.doi.org/10.1016/j.trsl.2019.02.010] [PMID: 30876809]

[12]
Mack, M. Inflammation and fibrosis. Mat Biol.,  2018, 68-69, 106-121.
 [http://dx.doi.org/10.1016/j.matbio.2017.11.010]

[13]
Faezi, S.T.; Paragomi, P.; Shahali, A.; Akhlaghkhah, M.; Akbarian, M.; Akhlaghi, M.; Kheirandish, M.; Gharibdoost, F. Prevalence and severity of depression and anxiety in patients with systemic sclerosis. J. Clin. Rheumatol.,  2017, 23(2), 80-86.
 [http://dx.doi.org/10.1097/RHU.0000000000000428] [PMID: 28099215]

[14]
Bejjani, F.; Evanno, E.; Zibara, K.; Piechaczyk, M.; Jariel-Encontre, I. The AP-1 transcriptional complex: Local switch or remote command? Biochim. Biophys. Acta Rev. Cancer,  2019, 1872(1), 11-23.
 [http://dx.doi.org/10.1016/j.bbcan.2019.04.003] [PMID: 31034924]

[15]
Eferl, R.; Wagner, E.F. AP-1: A double-edged sword in tumorigenesis. Nat. Rev. Cancer,  2003, 3(11), 859-868.
 [http://dx.doi.org/10.1038/nrc1209] [PMID: 14668816]

[16]
Hess, J.; Angel, P.; Schorpp-Kistner, M. AP-1 subunits: Quarrel and harmony among siblings. J. Cell Sci.,  2004, 117(25), 5965-5973.
 [http://dx.doi.org/10.1242/jcs.01589] [PMID: 15564374]

[17]
Chang, L.; Karin, M. Mammalian MAP kinase signalling cascades. Nature,  2001, 410(6824), 37-40.
 [http://dx.doi.org/10.1038/35065000] [PMID: 11242034]

[18]
Konishi, N.; Narita, Y.; Hijioka, F.; Masud, H.M.A.A.; Sato, Y.; Kimura, H.; Murata, T. BGLF2 increases infectivity of epstein-barr virus by activating AP-1 upon De Novo infection. MSphere,  2018, 3(2), e00138-18.
 [http://dx.doi.org/10.1128/mSphere.00138-18] [PMID: 29695622]

[19]
Bogoyevitch, M.A.; Kobe, B. Uses for JNK: The many and varied substrates of the c-Jun N-terminal kinases. Microbiol. Mol. Biol. Rev.,  2006, 70(4), 1061-1095.
 [http://dx.doi.org/10.1128/MMBR.00025-06] [PMID: 17158707]

[20]
Gallo, A.; Cuozzo, C.; Esposito, I.; Maggiolini, M.; Bonofiglio, D.; Vivacqua, A.; Garramone, M.; Weiss, C.; Bohmann, D.; Musti, A.M. Menin uncouples Elk-1, JunD and c-Jun phosphorylation from MAP kinase activation. Oncogene,  2002, 21(42), 6434-6445.
 [http://dx.doi.org/10.1038/sj.onc.1205822] [PMID: 12226747]

[21]
Lu, N.; Malemud, C.J. Extracellular signal-regulated kinase: A regulator of cell growth, inflammation, chondrocyte and bone cell receptor-mediated gene expression. Int. J. Mol. Sci.,  2019, 20(15), 3792.
 [http://dx.doi.org/10.3390/ijms20153792] [PMID: 31382554]

[22]
Reich, N.; Maurer, B.; Akhmetshina, A.; Venalis, P.; Dees, C.; Zerr, P.; Palumbo, K.; Zwerina, J.; Nevskaya, T.; Gay, S.; Distler, O.; Schett, G.; Distler, J.H.W. The transcription factor Fra-2 regulates the production of extracellular matrix in systemic sclerosis. Arthritis Rheum.,  2010, 62(1), 280-290.
 [http://dx.doi.org/10.1002/art.25056] [PMID: 20039427]

[23]
Avouac, J.; Palumbo, K.; Tomcik, M.; Zerr, P.; Dees, C.; Horn, A.; Maurer, B.; Akhmetshina, A.; Beyer, C.; Sadowski, A.; Schneider, H.; Shiozawa, S.; Distler, O.; Schett, G.; Allanore, Y.; Distler, J.H.W. Inhibition of activator protein 1 signaling abrogates transforming growth factor β-mediated activation of fibroblasts and prevents experimental fibrosis. Arthritis Rheum.,  2012, 64(5), 1642-1652.
 [http://dx.doi.org/10.1002/art.33501] [PMID: 22139817]

[24]
Palumbo, K.; Zerr, P.; Tomcik, M.; Vollath, S.; Dees, C.; Akhmetshina, A.; Avouac, J.; Yaniv, M.; Distler, O.; Schett, G.; Distler, J.H.W. The transcription factor JunD mediates transforming growth factor -induced fibroblast activation and fibrosis in systemic sclerosis. Ann. Rheum. Dis.,  2011, 70(7), 1320-1326.
 [http://dx.doi.org/10.1136/ard.2010.148296] [PMID: 21515915]

[25]
Sun, T.; Huang, Z.; Liang, W.C.; Yin, J.; Lin, W.Y.; Wu, J.; Vernes, J.M.; Lutman, J.; Caplazi, P.; Jeet, S.; Wong, T.; Wong, M.; DePianto, D.J.; Morshead, K.B.; Sun, K.H.; Modrusan, Z.; Vander Heiden, J.A.; Abbas, A.R.; Zhang, H.; Xu, M.; N’Diaye, E.N.; Roose-Girma, M.; Wolters, P.J.; Yadav, R.; Sukumaran, S.; Ghilardi, N.; Corpuz, R.; Emson, C.; Meng, Y.G.; Ramalingam, T.R.; Lupardus, P.; Brightbill, H.D.; Seshasayee, D.; Wu, Y.; Arron, J.R. TGFβ2 and TGFβ3 isoforms drive fibrotic disease pathogenesis. Sci. Transl. Med.,  2021, 13(605), eabe0407.
 [http://dx.doi.org/10.1126/scitranslmed.abe0407] [PMID: 34349032]

[26]
Budi, E.H.; Schaub, J.R.; Decaris, M.; Turner, S.; Derynck, R. TGF-β as a driver of fibrosis: Physiological roles and therapeutic opportunities. J. Pathol.,  2021, 254(4), 358-373.
 [http://dx.doi.org/10.1002/path.5680] [PMID: 33834494]

[27]
Tzavlaki, K.; Moustakas, A. TGF-β Signaling. Biomolecules,  2020, 10(3), 487.
 [http://dx.doi.org/10.3390/biom10030487] [PMID: 32210029]

[28]
Lu, M.; Qin, Q.; Yao, J.; Sun, L.; Qin, X. Induction of LOX by TGF-β1/Smad/AP-1 signaling aggravates rat myocardial fibrosis and heart failure. IUBMB Life,  2019, 71(11), 1729-1739.
 [http://dx.doi.org/10.1002/iub.2112] [PMID: 31317653]

[29]
Mallano, T.; Palumbo-Zerr, K.; Zerr, P.; Ramming, A.; Zeller, B.; Beyer, C.; Dees, C.; Huang, J.; Hai, T.; Distler, O.; Schett, G.; Distler, J.H.W. Activating transcription factor 3 regulates canonical TGFβ signalling in systemic sclerosis. Ann. Rheum. Dis.,  2016, 75(3), 586-592.
 [http://dx.doi.org/10.1136/annrheumdis-2014-206214] [PMID: 25589515]

[30]
Wang, J.; Sun, D.; Wang, Y.; Ren, F.; Pang, S.; Wang, D.; Xu, S. FOSL2 positively regulates TGF-β1 signalling in non-small cell lung cancer. PLoS One,  2014, 9(11), e112150.
 [http://dx.doi.org/10.1371/journal.pone.0112150] [PMID: 25375657]

[31]
Yao, C.D.; Haensel, D.; Gaddam, S.; Patel, T.; Atwood, S.X.; Sarin, K.Y.; Whitson, R.J.; McKellar, S.; Shankar, G.; Aasi, S.; Rieger, K.; Oro, A.E. AP-1 and TGFß cooperativity drives non-canonical Hedgehog signaling in resistant basal cell carcinoma. Nat. Commun.,  2020, 11(1), 5079.
 [http://dx.doi.org/10.1038/s41467-020-18762-5] [PMID: 33033234]

[32]
Hussain, S.; Khan, A.W.; Akhmedov, A.; Suades, R.; Costantino, S.; Paneni, F.; Caidahl, K.; Mohammed, S.A.; Hage, C.; Gkolfos, C.; Björck, H.; Pernow, J.; Lund, L.H.; Lüscher, T.F.; Cosentino, F. Hyperglycemia induces myocardial dysfunction via epigenetic regulation of JunD. Circ. Res.,  2020, 127(10), 1261-1273.
 [http://dx.doi.org/10.1161/CIRCRESAHA.120.317132] [PMID: 32815777]

[33]
Fu, L.; Peng, S.; Wu, W.; Ouyang, Y.; Tan, D.; Fu, X. LncRNA HOTAIRM1 promotes osteogenesis by controlling JNK/AP-1 signalling-mediated RUNX2 expression. J. Cell. Mol. Med.,  2019, 23(11), 7517-7524.
 [http://dx.doi.org/10.1111/jcmm.14620] [PMID: 31512358]

[34]
Lundgaard Donovan, L.; Henningsen, K.; Flou Kristensen, A.; Wiborg, O.; Nieland, J.D.; Lichota, J. Maternal separation followed by chronic mild stress in adulthood is associated with concerted epigenetic regulation of AP-1 complex genes. J. Pers. Med.,  2021, 11(3), 209.
 [http://dx.doi.org/10.3390/jpm11030209] [PMID: 33809485]

[35]
Kim, E.; Ahuja, A.; Kim, M.Y.; Cho, J.Y. DNA or protein methylation-dependent regulation of activator protein-1 function. Cells,  2021, 10(2), 461.
 [http://dx.doi.org/10.3390/cells10020461] [PMID: 33670008]

[36]
Casalino, L.; Talotta, F.; Cimmino, A.; Verde, P. The Fra-1/AP-1 oncoprotein: From the “Undruggable” transcription factor to therapeutic targeting. Cancers (Basel),  2022, 14(6), 1480.
 [http://dx.doi.org/10.3390/cancers14061480] [PMID: 35326630]

[37]
Talotta, F.; Casalino, L.; Verde, P. The nuclear oncoprotein Fra-1: A transcription factor knocking on therapeutic applications’ door. Oncogene,  2020, 39(23), 4491-4506.
 [http://dx.doi.org/10.1038/s41388-020-1306-4] [PMID: 32385348]

[38]
Li, L.; Yang, H.; He, Y.; Li, T.; Feng, J.; Chen, W.; Ao, L.; Shi, X.; Lin, Y.; Liu, H.; Zheng, E.; Lin, Q.; Bu, J.; Zeng, Y.; Zheng, M.; Xu, Y.; Liao, Z.; Lin, J.; Lin, D. Ubiquitin-specific protease USP6 regulates the stability of the c-Jun protein. Mol. Cell. Biol.,  2018, 38(2), e00320-17.
 [http://dx.doi.org/10.1128/MCB.00320-17] [PMID: 29061731]

[39]
Pakay, J.L.; Diesch, J.; Gilan, O.; Yip, Y-Y.; Sayan, E.; Kolch, W.; Mariadason, J.M.; Hannan, R.D.; Tulchinsky, E.; Dhillon, A.S. A 19S proteasomal subunit cooperates with an ERK MAPK-regulated degron to regulate accumulation of Fra-1 in tumour cells. Oncogene,  2012, 31(14), 1817-1824.
 [http://dx.doi.org/10.1038/onc.2011.375] [PMID: 21874050]

[40]
Lederer, D.J.; Martinez, F.J. Idiopathic pulmonary fibrosis. N. Engl. J. Med.,  2018, 378(19), 1811-1823.
 [http://dx.doi.org/10.1056/NEJMra1705751] [PMID: 29742380]

[41]
Wolters, P.J.; Collard, H.R.; Jones, K.D. Pathogenesis of idiopathic pulmonary fibrosis. Annu. Rev. Pathol.,  2014, 9(1), 157-179.
 [http://dx.doi.org/10.1146/annurev-pathol-012513-104706] [PMID: 24050627]

[42]
Wygrecka, M.; Zakrzewicz, D.; Taborski, B.; Didiasova, M.; Kwapiszewska, G.; Preissner, K.T.; Markart, P. TGF-β1 induces tissue factor expression in human lung fibroblasts in a PI3K/JNK/Akt-dependent and AP-1-dependent manner. Am. J. Respir. Cell Mol. Biol.,  2012, 47(5), 614-627.
 [http://dx.doi.org/10.1165/rcmb.2012-0097OC] [PMID: 22771387]

[43]
Ucero, A.C.; Bakiri, L.; Roediger, B.; Suzuki, M.; Jimenez, M.; Mandal, P.; Braghetta, P.; Bonaldo, P.; Paz-Ares, L.; Fustero-Torre, C.; Ximenez-Embun, P.; Hernandez, A.I.; Megias, D.; Wagner, E.F. Fra-2–expressing macrophages promote lung fibrosis. J. Clin. Invest.,  2019, 129(8), 3293-3309.
 [http://dx.doi.org/10.1172/JCI125366] [PMID: 31135379]

[44]
Eferl, R.; Hasselblatt, P.; Rath, M.; Popper, H.; Zenz, R.; Komnenovic, V.; Idarraga, M.H.; Kenner, L.; Wagner, E.F. Development of pulmonary fibrosis through a pathway involving the transcription factor Fra-2/AP-1. Proc. Natl. Acad. Sci. USA,  2008, 105(30), 10525-10530.
 [http://dx.doi.org/10.1073/pnas.0801414105] [PMID: 18641127]

[45]
Avouac, J.; Konstantinova, I.; Guignabert, C.; Pezet, S.; Sadoine, J.; Guilbert, T.; Cauvet, A.; Tu, L.; Luccarini, J.M.; Junien, J.L.; Broqua, P.; Allanore, Y. Pan-PPAR agonist IVA337 is effective in experimental lung fibrosis and pulmonary hypertension. Ann. Rheum. Dis.,  2017, 76(11), 1931-1940.
 [http://dx.doi.org/10.1136/annrheumdis-2016-210821] [PMID: 28801346]

[46]
Schnieder, J; Mamazhakypov, A; Birnhuber, A; Wilhelm, J; Kwapiszewska, G; Ruppert, C Loss of LRP1 promotes acquisition of contractile-myofibroblast phenotype and release of active TGF-β1 from ECM stores. Matrix Biol. J. Int. Soc. Matrix Biol., 2020.
 [http://dx.doi.org/10.1016/j.matbio.2019.12.001]

[47]
Tabeling, C.; Wienhold, S.M.; Birnhuber, A.; Brack, M.C.; Nouailles, G.; Kershaw, O.; Firsching, T.C.; Gruber, A.D.; Lienau, J.; Marsh, L.M.; Olschewski, A.; Kwapiszewska, G.; Witzenrath, M. Pulmonary fibrosis in Fra-2 transgenic mice is associated with decreased numbers of alveolar macrophages and increased susceptibility to pneumococcal pneumonia. Am. J. Physiol. Lung Cell. Mol. Physiol.,  2021, 320(5), L916-L925.
 [http://dx.doi.org/10.1152/ajplung.00505.2020] [PMID: 33655757]

[48]
Birnhuber, A.; Biasin, V.; Schnoegl, D.; Marsh, L.M.; Kwapiszewska, G. Transcription factor Fra-2 and its emerging role in matrix deposition, proliferation and inflammation in chronic lung diseases. Cell. Signal.,  2019, 64, 109408.
 [http://dx.doi.org/10.1016/j.cellsig.2019.109408] [PMID: 31473307]

[49]
Deng, X.; Xu, M.; Yuan, C.; Yin, L.; Chen, X.; Zhou, X.; Li, G.; Fu, Y.; Feghali-Bostwick, C.A.; Pang, L. Transcriptional regulation of increased CCL2 expression in pulmonary fibrosis involves nuclear factor-κB and activator protein-1. Int. J. Biochem. Cell Biol.,  2013, 45(7), 1366-1376.
 [http://dx.doi.org/10.1016/j.biocel.2013.04.003] [PMID: 23583295]

[50]
Klymenko, O.; Huehn, M.; Wilhelm, J.; Wasnick, R.; Shalashova, I.; Ruppert, C.; Henneke, I.; Hezel, S.; Guenther, K.; Mahavadi, P.; Samakovlis, C.; Seeger, W.; Guenther, A.; Korfei, M. Regulation and role of the ER stress transcription factor CHOP in alveolar epithelial type-II cells. J. Mol. Med. (Berl.),  2019, 97(7), 973-990.
 [http://dx.doi.org/10.1007/s00109-019-01787-9] [PMID: 31025089]

[51]
Oruqaj, G.; Karnati, S.; Vijayan, V.; Kotarkonda, L.K.; Boateng, E.; Zhang, W.; Ruppert, C.; Günther, A.; Shi, W.; Baumgart-Vogt, E. Compromised peroxisomes in idiopathic pulmonary fibrosis, a vicious cycle inducing a higher fibrotic response via TGF-β signaling. Proc. Natl. Acad. Sci. USA,  2015, 112(16), E2048-E2057.
 [http://dx.doi.org/10.1073/pnas.1415111112] [PMID: 25848047]

[52]
Rajasekaran, S.; Reddy, N.M.; Zhang, W.; Reddy, S.P. Expression profiling of genes regulated by Fra-1/AP-1 transcription factor during bleomycin-induced pulmonary fibrosis. BMC Genomics,  2013, 14(1), 381.
 [http://dx.doi.org/10.1186/1471-2164-14-381] [PMID: 23758685]

[53]
Rajasekaran, S.; Vaz, M.; Reddy, S.P. Fra-1/AP-1 transcription factor negatively regulates pulmonary fibrosis in vivo. PLoS One,  2012, 7(7), e41611.
 [http://dx.doi.org/10.1371/journal.pone.0041611] [PMID: 22911824]

[54]
Allanore, Y.; Simms, R.; Distler, O.; Trojanowska, M.; Pope, J.; Denton, C.P.; Varga, J. Systemic sclerosis. Nat. Rev. Dis. Primers,  2015, 1(1), 15002.
 [http://dx.doi.org/10.1038/nrdp.2015.2] [PMID: 27189141]

[55]
Kumar, S.; Singh, J.; Rattan, S.; DiMarino, A.J.; Cohen, S.; Jimenez, S.A. Review article: Pathogenesis and clinical manifestations of gastrointestinal involvement in systemic sclerosis. Aliment. Pharmacol. Ther.,  2017, 45(7), 883-898.
 [http://dx.doi.org/10.1111/apt.13963] [PMID: 28185291]

[56]
Tyndall, A.J.; Bannert, B.; Vonk, M.; Airò, P.; Cozzi, F.; Carreira, P.E.; Bancel, D.F.; Allanore, Y.; Müller-Ladner, U.; Distler, O.; Iannone, F.; Pellerito, R.; Pileckyte, M.; Miniati, I.; Ananieva, L.; Gurman, A.B.; Damjanov, N.; Mueller, A.; Valentini, G.; Riemekasten, G.; Tikly, M.; Hummers, L.; Henriques, M.J.; Caramaschi, P.; Scheja, A.; Rozman, B.; Ton, E.; Kumánovics, G.; Coleiro, B.; Feierl, E.; Szucs, G.; Von Mühlen, C.A.; Riccieri, V.; Novak, S.; Chizzolini, C.; Kotulska, A.; Denton, C.; Coelho, P.C.; Kötter, I.; Simsek, I.; de la Pena Lefebvre, P.G.; Hachulla, E.; Seibold, J.R.; Rednic, S.; Stork, J.; Morovic-Vergles, J.; Walker, U.A. Causes and risk factors for death in systemic sclerosis: A study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann. Rheum. Dis.,  2010, 69(10), 1809-1815.
 [http://dx.doi.org/10.1136/ard.2009.114264] [PMID: 20551155]

[57]
Maurer, B.; Distler, J.H.W.; Distler, O. The Fra-2 transgenic mouse model of systemic sclerosis. Vascul. Pharmacol.,  2013, 58(3), 194-201.
 [http://dx.doi.org/10.1016/j.vph.2012.12.001] [PMID: 23232070]

[58]
Dees, C.; Pötter, S.; Zhang, Y.; Bergmann, C.; Zhou, X.; Luber, M.; Wohlfahrt, T.; Karouzakis, E.; Ramming, A.; Gelse, K.; Yoshimura, A.; Jaenisch, R.; Distler, O.; Schett, G.; Distler, J.H.W. TGF-β–induced epigenetic deregulation of SOCS3 facilitates STAT3 signaling to promote fibrosis. J. Clin. Invest.,  2020, 130(5), 2347-2363.
 [http://dx.doi.org/10.1172/JCI122462] [PMID: 31990678]

[59]
Cutolo, M.; Soldano, S.; Smith, V. Pathophysiology of systemic sclerosis: current understanding and new insights. Expert Rev. Clin. Immunol.,  2019, 15(7), 753-764.
 [http://dx.doi.org/10.1080/1744666X.2019.1614915] [PMID: 31046487]

[60]
Tsou, P.S.; Varga, J.; O’Reilly, S. Advances in epigenetics in systemic sclerosis: Molecular mechanisms and therapeutic potential. Nat. Rev. Rheumatol.,  2021, 17(10), 596-607.
 [http://dx.doi.org/10.1038/s41584-021-00683-2] [PMID: 34480165]

[61]
Kizilay Mancini, O.; Acevedo, M.; Fazez, N.; Cuillerier, A.; Fernandez Ruiz, A.; Huynh, D.N.; Burelle, Y.; Ferbeyre, G.; Baron, M.; Servant, M.J. Oxidative stress-induced senescence mediates inflammatory and fibrotic phenotypes in fibroblasts from systemic sclerosis patients. Rheumatology (Oxford),  2022, 61(3), 1265-1275.
 [http://dx.doi.org/10.1093/rheumatology/keab477] [PMID: 34115840]

[62]
Ponticos, M.; Papaioannou, I.; Xu, S.; Holmes, A.M.; Khan, K.; Denton, C.P.; Bou-Gharios, G.; Abraham, D.J. Failed degradation of JunB contributes to overproduction of type I collagen and development of dermal fibrosis in patients with systemic sclerosis. Arthritis Rheumatol.,  2015, 67(1), 243-253.
 [http://dx.doi.org/10.1002/art.38897] [PMID: 25303440]

[63]
Bergmann, C.; Brandt, A.; Merlevede, B.; Hallenberger, L.; Dees, C.; Wohlfahrt, T.; Pötter, S.; Zhang, Y.; Chen, C.W.; Mallano, T.; Liang, R.; Kagwiria, R.; Kreuter, A.; Pantelaki, I.; Bozec, A.; Abraham, D.; Rieker, R.; Ramming, A.; Distler, O.; Schett, G.; Distler, J.H.W. The histone demethylase Jumonji domain-containing protein 3 (JMJD3) regulates fibroblast activation in systemic sclerosis. Ann. Rheum. Dis.,  2018, 77(1), 150-158.
 [http://dx.doi.org/10.1136/annrheumdis-2017-211501] [PMID: 29070530]

[64]
Krämer, M.; Dees, C.; Huang, J.; Schlottmann, I.; Palumbo-Zerr, K.; Zerr, P.; Gelse, K.; Beyer, C.; Distler, A.; Marquez, V.E.; Distler, O.; Schett, G.; Distler, J.H.W. Inhibition of H3K27 histone trimethylation activates fibroblasts and induces fibrosis. Ann. Rheum. Dis.,  2013, 72(4), 614-620.
 [http://dx.doi.org/10.1136/annrheumdis-2012-201615] [PMID: 22915621]

[65]
Cui, N.; Hu, M.; Khalil, R.A. Biochemical and biological attributes of matrix metalloproteinases. Prog. Mol. Biol. Transl. Sci.,  2017, 147, 1-73.
 [http://dx.doi.org/10.1016/bs.pmbts.2017.02.005] [PMID: 28413025]

[66]
Ciechomska, M.; O’Reilly, S.; Przyborski, S.; Oakley, F.; Bogunia-Kubik, K.; van Laar, J.M. Histone demethylation and toll-like receptor 8-dependent cross-talk in monocytes promotes transdifferentiation of fibroblasts in systemic sclerosis via Fra-2. Arthritis Rheumatol.,  2016, 68(6), 1493-1504.
 [http://dx.doi.org/10.1002/art.39602] [PMID: 26814616]

[67]
Maurer, B.; Reich, N.; Juengel, A.; Kriegsmann, J.; Gay, R.E.; Schett, G.; Michel, B.A.; Gay, S.; Distler, J.H.W.; Distler, O. Fra-2 transgenic mice as a novel model of pulmonary hypertension associated with systemic sclerosis. Ann. Rheum. Dis.,  2012, 71(8), 1382-1387.
 [http://dx.doi.org/10.1136/annrheumdis-2011-200940] [PMID: 22523431]

[68]
Venalis, P.; Kumánovics, G.; Schulze-Koops, H.; Distler, A.; Dees, C.; Zerr, P.; Palumbo-Zerr, K.; Czirják, L.; Mackevic, Z.; Lundberg, I.E.; Distler, O.; Schett, G.; Distler, J.H.W. Cardiomyopathy in murine models of systemic sclerosis. Arthritis Rheumatol.,  2015, 67(2), 508-516.
 [http://dx.doi.org/10.1002/art.38942] [PMID: 25371068]

[69]
Schuppan, D.; Kim, Y.O. Evolving therapies for liver fibrosis. J. Clin. Invest.,  2013, 123(5), 1887-1901.
 [http://dx.doi.org/10.1172/JCI66028] [PMID: 23635787]

[70]
Hernandez-Gea, V.; Friedman, S.L. Pathogenesis of liver fibrosis. Annu. Rev. Pathol.,  2011, 6(1), 425-456.
 [http://dx.doi.org/10.1146/annurev-pathol-011110-130246] [PMID: 21073339]

[71]
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]

[72]
Lachowski, D.; Cortes, E.; Rice, A.; Pinato, D.; Rombouts, K.; del Rio Hernandez, A. Matrix stiffness modulates the activity of MMP-9 and TIMP-1 in hepatic stellate cells to perpetuate fibrosis. Sci. Rep.,  2019, 9(1), 7299.
 [http://dx.doi.org/10.1038/s41598-019-43759-6] [PMID: 31086224]

[73]
Smart, D.E.; Vincent, K.J.; Arthur, M.J.P.; Eickelberg, O.; Castellazzi, M.; Mann, J.; Mann, D.A. JunD regulates transcription of the tissue inhibitor of metalloproteinases-1 and interleukin-6 genes in activated hepatic stellate cells. J. Biol. Chem.,  2001, 276(26), 24414-24421.
 [http://dx.doi.org/10.1074/jbc.M101840200] [PMID: 11337499]

[74]
Moschen, A.R.; Fritz, T.; Clouston, A.D.; Rebhan, I.; Bauhofer, O.; Barrie, H.D.; Powell, E.E.; Kim, S.H.; Dinarello, C.A.; Bartenschlager, R.; Jonsson, J.R.; Tilg, H. Interleukin-32: A new proinflammatory cytokine involved in hepatitis C virus-related liver inflammation and fibrosis. Hepatology,  2011, 53(6), 1819-1829.
 [http://dx.doi.org/10.1002/hep.24285] [PMID: 21381070]

[75]
Xu, H.; Zhang, S.; Pan, X.; Cao, H.; Huang, X.; Xu, Q.; Zhong, H.; Peng, X. TIMP-1 expression induced by IL-32 is mediated through activation of AP-1 signal pathway. Int. Immunopharmacol.,  2016, 38, 233-237.
 [http://dx.doi.org/10.1016/j.intimp.2016.06.002] [PMID: 27302771]

[76]
Surina, S.; Fontanella, R.A.; Scisciola, L.; Marfella, R.; Paolisso, G.; Barbieri, M. miR-21 in Human Cardiomyopathies. Front. Cardiovasc. Med.,  2021, 8, 767064.
 [http://dx.doi.org/10.3389/fcvm.2021.767064] [PMID: 34778418]

[77]
Sun, J.; Shi, L.; Xiao, T.; Xue, J.; Li, J.; Wang, P.; Wu, L.; Dai, X.; Ni, X.; Liu, Q. microRNA-21, via the HIF-1α/VEGF signaling pathway, is involved in arsenite-induced hepatic fibrosis through aberrant cross-talk of hepatocytes and hepatic stellate cells. Chemosphere,  2021, 266, 129177.
 [http://dx.doi.org/10.1016/j.chemosphere.2020.129177] [PMID: 33310519]

[78]
Zhang, Z.; Zha, Y.; Hu, W.; Huang, Z.; Gao, Z.; Zang, Y.; Chen, J.; Dong, L.; Zhang, J. The autoregulatory feedback loop of microRNA-21/programmed cell death protein 4/activation protein-1 (MiR-21/PDCD4/AP-1) as a driving force for hepatic fibrosis development. J. Biol. Chem.,  2013, 288(52), 37082-37093.
 [http://dx.doi.org/10.1074/jbc.M113.517953] [PMID: 24196965]

[79]
Ye, Y; Dan, Z. All-trans retinoic acid diminishes collagen production in a hepatic stellate cell line via suppression of active protein-1 and c-Jun N-terminal kinase signal J Huazhong Univ Sci Technolog Med Sci.,  2010, 30(6), 726-733.
 [http://dx.doi.org/10.1007/s11596-010-0648-5]

[80]
Dorn, C.; Engelmann, J.C.; Saugspier, M.; Koch, A.; Hartmann, A.; Müller, M.; Spang, R.; Bosserhoff, A.; Hellerbrand, C. Increased expression of c-Jun in nonalcoholic fatty liver disease. Lab. Invest.,  2014, 94(4), 394-408.
 [http://dx.doi.org/10.1038/labinvest.2014.3] [PMID: 24492282]

[81]
Schulien, I.; Hockenjos, B.; Schmitt-Graeff, A.; Perdekamp, M.G.; Follo, M.; Thimme, R.; Hasselblatt, P. The transcription factor c-Jun/AP-1 promotes liver fibrosis during non-alcoholic steatohepatitis by regulating Osteopontin expression. Cell Death Differ.,  2019, 26(9), 1688-1699.
 [http://dx.doi.org/10.1038/s41418-018-0239-8] [PMID: 30778201]

[82]
Kireva, T.; Erhardt, A.; Tiegs, G.; Tilg, H.; Denk, H.; Haybaeck, J.; Aigner, E.; Moschen, A.; Distler, J.H.; Schett, G.; Zwerina, J. Transcription factor Fra-1 induces cholangitis and liver fibrosis. Hepatology,  2011, 53(4), 1287-1297.
 [http://dx.doi.org/10.1002/hep.24175] [PMID: 21480331]

[83]
Hasenfuss, S.C.; Bakiri, L.; Thomsen, M.K.; Hamacher, R.; Wagner, E.F. Activator protein 1 transcription factor fos-related antigen 1 (fra-1) is dispensable for murine liver fibrosis, but modulates xenobiotic metabolism. Hepatology,  2014, 59(1), 261-273.
 [http://dx.doi.org/10.1002/hep.26518] [PMID: 23703832]

[84]
Zhuang, S.; Hua, X.; He, K.; Zhou, T.; Zhang, J.; Wu, H.; Ma, X.; Xia, Q.; Zhang, J. Inhibition of GSK-3β induces AP-1-mediated osteopontin expression to promote cholestatic liver fibrosis. FASEB J.,  2018, 32(8), 4494-4503.
 [http://dx.doi.org/10.1096/fj.201701137R] [PMID: 29529390]

[85]
Ginès, P.; Krag, A.; Abraldes, J.G.; Solà, E.; Fabrellas, N.; Kamath, P.S. Liver cirrhosis. Lancet,  2021, 398(10308), 1359-1376.
 [http://dx.doi.org/10.1016/S0140-6736(21)01374-X] [PMID: 34543610]

[86]
Gyöngyösi, M.; Winkler, J.; Ramos, I.; Do, Q.T.; Firat, H.; McDonald, K.; González, A.; Thum, T.; Díez, J.; Jaisser, F.; Pizard, A.; Zannad, F. Myocardial fibrosis: biomedical research from bench to bedside. Eur. J. Heart Fail.,  2017, 19(2), 177-191.
 [http://dx.doi.org/10.1002/ejhf.696] [PMID: 28157267]

[87]
Frangogiannis, N.G. Cardiac fibrosis. Cardiovasc. Res.,  2021, 117(6), 1450-1488.
 [http://dx.doi.org/10.1093/cvr/cvaa324] [PMID: 33135058]

[88]
Philips, N.; Bashey, R.I.; Jiménez, S.A. Increased alpha 1(I) procollagen gene expression in tight skin (TSK) mice myocardial fibroblasts is due to a reduced interaction of a negative regulatory sequence with AP-1 transcription factor. J. Biol. Chem.,  1995, 270(16), 9313-9321.
 [http://dx.doi.org/10.1074/jbc.270.16.9313] [PMID: 7721853]

[89]
Schröder, D.; Heger, J.; Piper, H.M.; Euler, G. Angiotensin II stimulates apoptosis via TGF-β1 signaling in ventricular cardiomyocytes of rat. J. Mol. Med. (Berl.),  2006, 84(11), 975-983.
 [http://dx.doi.org/10.1007/s00109-006-0090-0] [PMID: 16924465]

[90]
Lorenzen, J.M.; Schauerte, C.; Hübner, A.; Kölling, M.; Martino, F.; Scherf, K.; Batkai, S.; Zimmer, K.; Foinquinos, A.; Kaucsar, T.; Fiedler, J.; Kumarswamy, R.; Bang, C.; Hartmann, D.; Gupta, S.K.; Kielstein, J.; Jungmann, A.; Katus, H.A.; Weidemann, F.; Müller, O.J.; Haller, H.; Thum, T. Osteopontin is indispensible for AP1-mediated angiotensin II-related miR-21 transcription during cardiac fibrosis. Eur. Heart J.,  2015, 36(32), 2184-2196.
 [http://dx.doi.org/10.1093/eurheartj/ehv109] [PMID: 25898844]

[91]
López, B.; González, A.; Hermida, N.; Valencia, F.; de Teresa, E.; Díez, J. Role of lysyl oxidase in myocardial fibrosis: From basic science to clinical aspects. Am. J. Physiol. Heart Circ. Physiol.,  2010, 299(1), H1-H9.
 [http://dx.doi.org/10.1152/ajpheart.00335.2010] [PMID: 20472764]

[92]
Seidenberg, J.; Stellato, M.; Hukara, A.; Ludewig, B.; Klingel, K.; Distler, O.; Błyszczuk, P.; Kania, G. The AP-1 transcription factor Fosl-2 regulates autophagy in cardiac fibroblasts during myocardial fibrogenesis. Int. J. Mol. Sci.,  2021, 22(4), 1861.
 [http://dx.doi.org/10.3390/ijms22041861] [PMID: 33668422]

[93]
Palomer, X.; Román-Azcona, M.S.; Pizarro-Delgado, J.; Planavila, A.; Villarroya, F.; Valenzuela-Alcaraz, B.; Crispi, F.; Sepúlveda-Martínez, Á.; Miguel-Escalada, I.; Ferrer, J.; Nistal, J.F.; García, R.; Davidson, M.M.; Barroso, E.; Vázquez-Carrera, M. SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation. Signal Transduct. Target. Ther.,  2020, 5(1), 14.
 [http://dx.doi.org/10.1038/s41392-020-0114-1] [PMID: 32296036]

[94]
Kleeff, J.; Whitcomb, D.C.; Shimosegawa, T.; Esposito, I.; Lerch, M.M.; Gress, T.; Mayerle, J.; Drewes, A.M.; Rebours, V.; Akisik, F.; Muñoz, J.E.D.; Neoptolemos, J.P. Chronic pancreatitis. Nat. Rev. Dis. Primers,  2017, 3(1), 17060.
 [http://dx.doi.org/10.1038/nrdp.2017.60] [PMID: 28880010]

[95]
Bynigeri, R.R.; Jakkampudi, A.; Jangala, R.; Subramanyam, C.; Sasikala, M.; Rao, G.V.; Reddy, D.N.; Talukdar, R. Pancreatic stellate cell: Pandora’s box for pancreatic disease biology. World J. Gastroenterol.,  2017, 23(3), 382-405.
 [http://dx.doi.org/10.3748/wjg.v23.i3.382] [PMID: 28210075]

[96]
Fitzner, B.; Sparmann, G.; Emmrich, J.; Liebe, S.; Jaster, R. Involvement of AP-1 proteins in pancreatic stellate cell activation in vitro. Int. J. Colorectal Dis.,  2004, 19(5), 414-420.
 [http://dx.doi.org/10.1007/s00384-003-0565-1] [PMID: 14727130]

[97]
An, W; Zhu, JW; Jiang, F; Jiang, H; Zhao, JL; Liu, MY Fibromodulin is upregulated by oxidative stress through the MAPK/AP-1 pathway to promote pancreatic stellate cell activation Pancreatology.,  2020, 20(2), 278-287.
 [http://dx.doi.org/10.1016/j.pan.2019.09.011]

[98]
Nastase, M.V.; Zeng-Brouwers, J.; Wygrecka, M.; Schaefer, L. Targeting renal fibrosis: Mechanisms and drug delivery systems. Adv. Drug Deliv. Rev.,  2018, 129, 295-307.
 [http://dx.doi.org/10.1016/j.addr.2017.12.019] [PMID: 29288033]

[99]
Tan, Y.; Cao, H.; Li, Q.; Sun, J. The role of transcription factor Ap1 in the activation of the Nrf2/ARE pathway through TET1 in diabetic nephropathy. Cell Biol. Int.,  2021, 45(8), 1654-1665.
 [http://dx.doi.org/10.1002/cbin.11599] [PMID: 33760331]

[100]
Urate, S.; Wakui, H.; Azushima, K.; Yamaji, T.; Suzuki, T.; Abe, E.; Tanaka, S.; Taguchi, S.; Tsukamoto, S.; Kinguchi, S.; Uneda, K.; Kanaoka, T.; Atobe, Y.; Funakoshi, K.; Yamashita, A.; Tamura, K. Aristolochic acid induces renal fibrosis and senescence in mice. Int. J. Mol. Sci.,  2021, 22(22), 12432.
 [http://dx.doi.org/10.3390/ijms222212432] [PMID: 34830314]

[101]
Rui, H.; Wang, Y.; Cheng, H.; Chen, Y. JNK-dependent AP-1 activation is required for aristolochic acid-induced TGF-β1 synthesis in human renal proximal epithelial cells. Am. J. Physiol. Renal Physiol.,  2012, 302(12), F1569-F1575.
 [http://dx.doi.org/10.1152/ajprenal.00560.2011] [PMID: 22442213]

[102]
Sun, Q.; Miao, J.; Luo, J.; Yuan, Q.; Cao, H.; Su, W.; Zhou, Y.; Jiang, L.; Fang, L.; Dai, C.; Zen, K.; Yang, J. The feedback loop between miR-21, PDCD4 and AP-1 functions as a driving force for renal fibrogenesis. J. Cell Sci.,  2018, 131(6), jcs202317.
 [http://dx.doi.org/10.1242/jcs.202317] [PMID: 29361523]

[103]
Gaedeke, J.; Noble, N.A.; Border, W.A. Curcumin blocks multiple sites of the TGF-β signaling cascade in renal cells. Kidney Int.,  2004, 66(1), 112-120.
 [http://dx.doi.org/10.1111/j.1523-1755.2004.00713.x] [PMID: 15200418]

[104]
Wang, H.N.; Ji, K.; Zhang, L.N.; Xie, C.C.; Li, W.Y.; Zhao, Z.F.; Chen, J.J. Inhibition of c-Fos expression attenuates IgE-mediated mast cell activation and allergic inflammation by counteracting an inhibitory AP1/Egr1/IL-4 axis. J. Transl. Med.,  2021, 19(1), 261.
 [http://dx.doi.org/10.1186/s12967-021-02932-0] [PMID: 34130714]

[105]
Choi, Y.; Jeon, H.; Akin, J.W.; Curry, T.E., Jr; Jo, M. The FOS/AP-1 regulates metabolic changes and cholesterol synthesis in human periovulatory granulosa cells. Endocrinology,  2021, 162(9), bqab127.
 [http://dx.doi.org/10.1210/endocr/bqab127] [PMID: 34171102]

[106]
Ye, N.; Ding, Y.; Wild, C.; Shen, Q.; Zhou, J. Small molecule inhibitors targeting activator protein 1 (AP-1). J. Med. Chem.,  2014, 57(16), 6930-6948.
 [http://dx.doi.org/10.1021/jm5004733] [PMID: 24831826]

[107]
Motomura, H.; Seki, S.; Shiozawa, S.; Aikawa, Y.; Nogami, M.; Kimura, T. A selective c-Fos/AP-1 inhibitor prevents cartilage destruction and subsequent osteophyte formation. Biochem. Biophys. Res. Commun.,  2018, 497(2), 756-761.
 [http://dx.doi.org/10.1016/j.bbrc.2018.02.147] [PMID: 29476740]

[108]
Ishida, M.; Ueki, M.; Morishita, J.; Ueno, M.; Shiozawa, S.; Maekawa, N. T-5224, a selective inhibitor of c-Fos/activator protein-1, improves survival by inhibiting serum high mobility group box-1 in lethal lipopolysaccharide-induced acute kidney injury model. J. Intensive Care,  2015, 3(1), 49.
 [http://dx.doi.org/10.1186/s40560-015-0115-2] [PMID: 26579229]

[109]
Kamide, D.; Yamashita, T.; Araki, K.; Tomifuji, M.; Tanaka, Y.; Tanaka, S.; Shiozawa, S.; Shiotani, A. Selective activator protein-1 inhibitor T-5224 prevents lymph node metastasis in an oral cancer model. Cancer Sci.,  2016, 107(5), 666-673.
 [http://dx.doi.org/10.1111/cas.12914] [PMID: 26918517]

[110]
Sohn, S.I.; Priya, A.; Balasubramaniam, B.; Muthuramalingam, P.; Sivasankar, C.; Selvaraj, A.; Valliammai, A.; Jothi, R.; Pandian, S. Biomedical applications and bioavailability of curcumin—an updated overview. Pharmaceutics,  2021, 13(12), 2102.
 [http://dx.doi.org/10.3390/pharmaceutics13122102] [PMID: 34959384]

[111]
Zorofchian Moghadamtousi, S.; Abdul Kadir, H.; Hassandarvish, P.; Tajik, H.; Abubakar, S.; Zandi, K. A review on antibacterial, antiviral, and antifungal activity of curcumin. BioMed Res. Int.,  2014, 2014, 1-12.
 [http://dx.doi.org/10.1155/2014/186864] [PMID: 24877064]

[112]
Abd Wahab, N.A.; Lajis, N.H.; Abas, F.; Othman, I.; Naidu, R. Mechanism of anti-cancer activity of curcumin on androgen-dependent and androgen-independent prostate cancer. Nutrients,  2020, 12(3), 679.
 [http://dx.doi.org/10.3390/nu12030679] [PMID: 32131560]

[113]
Kunnumakkara, A.B.; Anand, P.; Aggarwal, B.B. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett.,  2008, 269(2), 199-225.
 [http://dx.doi.org/10.1016/j.canlet.2008.03.009] [PMID: 18479807]

[114]
Bierhaus, A.; Zhang, Y.; Quehenberger, P.; Luther, T.; Haase, M.; Müller, M.; Mackman, N.; Ziegler, R.; Nawroth, P.P. The dietary pigment curcumin reduces endothelial tissue factor gene expression by inhibiting binding of AP-1 to the DNA and activation of NF-kappa B. Thromb. Haemost.,  1997, 77(4), 772-782.
 [http://dx.doi.org/10.1055/s-0038-1656049] [PMID: 9134658]

[115]
Huang, T.S.; Lee, S.C.; Lin, J.K. Suppression of c-Jun/AP-1 activation by an inhibitor of tumor promotion in mouse fibroblast cells. Proc. Natl. Acad. Sci. USA,  1991, 88(12), 5292-5296.
 [http://dx.doi.org/10.1073/pnas.88.12.5292] [PMID: 1905019]

[116]
Sullivan, D.E.; Ferris, M.; Nguyen, H.; Abboud, E.; Brody, A.R. TNF-α induces TGF-β 1 expression in lung fibroblasts at the transcriptional level via AP-1 activation. J. Cell. Mol. Med.,  2009, 13(8b), 1866-1876.
 [http://dx.doi.org/10.1111/j.1582-4934.2008.00647.x] [PMID: 20141610]

[117]
Masamune, A.; Suzuki, N.; Kikuta, K.; Satoh, M.; Satoh, K.; Shimosegawa, T. Curcumin blocks activation of pancreatic stellate cells. J. Cell. Biochem.,  2006, 97(5), 1080-1093.
 [http://dx.doi.org/10.1002/jcb.20698] [PMID: 16294327]

[118]
Huang, J.; Huang, K.; Lan, T.; Xie, X.; Shen, X.; Liu, P.; Huang, H. Curcumin ameliorates diabetic nephropathy by inhibiting the activation of the SphK1-S1P signaling pathway. Mol. Cell. Endocrinol.,  2013, 365(2), 231-240.
 [http://dx.doi.org/10.1016/j.mce.2012.10.024] [PMID: 23127801]

[119]
Patel, S.S.; Acharya, A.; Ray, R.S.; Agrawal, R.; Raghuwanshi, R.; Jain, P. Cellular and molecular mechanisms of curcumin in prevention and treatment of disease. Crit. Rev. Food Sci. Nutr.,  2020, 60(6), 887-939.
 [http://dx.doi.org/10.1080/10408398.2018.1552244] [PMID: 30632782]

[120]
Singh, R.; Kaundal, R.K.; Zhao, B.; Bouchareb, R.; Lebeche, D. Resistin induces cardiac fibroblast-myofibroblast differentiation through JAK/STAT3 and JNK/c-Jun signaling. Pharmacol. Res.,  2021, 167, 105414.
 [http://dx.doi.org/10.1016/j.phrs.2020.105414] [PMID: 33524540]

[121]
Liu, Y.; Cong, S.; Cheng, Z.; Hu, Y.; Lei, Y.; Zhu, L.; Zhao, X.; Mu, M.; Zhang, B.; Fan, L.; Yu, L.; Cheng, M. Platycodin D alleviates liver fibrosis and activation of hepatic stellate cells by regulating JNK/c-JUN signal pathway. Eur. J. Pharmacol.,  2020, 876, 172946.
 [http://dx.doi.org/10.1016/j.ejphar.2020.172946] [PMID: 31996320]

[122]
Wu, X; Shu, L; Zhang, Z; Li, J; Zong, J; Cheong, LY Adipocyte fatty acid binding protein promotes the onset and progression of liver fibrosis via mediating the crosstalk between liver sinusoidal endothelial cells and hepatic stellate cells. Advanced science,  2021, 8(11), e2003721.
 [http://dx.doi.org/10.1002/advs.202003721]

[123]
Jiang, M.; Fan, J.; Qu, X.; Li, S.; Nilsson, S.K.; Sun, Y.B.Y.; Chen, Y.; Yu, D.; Liu, D.; Liu, B.C.; Tang, M.; Chen, W.; Ren, Y.; Nikolic-Paterson, D.J.; Jiang, X.; Li, J.; Yu, X. Combined blockade of smad3 and jnk pathways ameliorates progressive fibrosis in folic acid nephropathy. Front. Pharmacol.,  2019, 10, 880.
 [http://dx.doi.org/10.3389/fphar.2019.00880] [PMID: 31447676]

[124]
Zhang, H.; Liu, X.; Zhou, S.; Jia, Y.; Li, Y.; Song, Y.; Wang, J.; Wu, H. SP600125 suppresses Keap1 expression and results in NRF2-mediated prevention of diabetic nephropathy. J. Mol. Endocrinol.,  2018, 60(2), 145-157.
 [http://dx.doi.org/10.1530/JME-17-0260] [PMID: 29273684]

[125]
Shen, D.; Cheng, H.; Cai, B.; Cai, W.; Wang, B.; Zhu, Q.; Wu, Y.; Liu, M.; Chen, R.; Gao, F.; Zhang, Y.; Niu, Y.; Shi, G. N-n-Butyl haloperidol iodide ameliorates liver fibrosis and hepatic stellate cell activation in mice. Acta Pharmacol. Sin.,  2022, 43(1), 133-145.
 [http://dx.doi.org/10.1038/s41401-021-00630-7] [PMID: 33758354]

[126]
Zhang, J.; Jiang, N.; Ping, J.; Xu, L. TGF-β1-induced autophagy activates hepatic stellate cells via the ERK and JNK signaling pathways. Int. J. Mol. Med.,  2020, 47(1), 256-266.
 [http://dx.doi.org/10.3892/ijmm.2020.4778] [PMID: 33236148]

[127]
Wu, G; Wang, Z; Shan, P; Huang, S; Lin, S; Huang, W Suppression of Netrin-1 attenuates angiotension II-induced cardiac remodeling through the PKC/MAPK signaling pathway. Biomedicine & pharmacotherapy,  2020, 130, 110495.
 [http://dx.doi.org/10.1016/j.biopha.2020.110495]

[128]
Kubczak, M.; Szustka, A.; Rogalińska, M. Molecular targets of natural compounds with anti-cancer properties. Int. J. Mol. Sci.,  2021, 22(24), 13659.
 [http://dx.doi.org/10.3390/ijms222413659] [PMID: 34948455]

[129]
Lee, W.; Haslinger, A.; Karin, M.; Tjian, R. Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40. Nature,  1987, 325(6102), 368-372.
 [http://dx.doi.org/10.1038/325368a0] [PMID: 3027570]

[130]
Brennan, A.; Leech, J.T.; Kad, N.M.; Mason, J.M. Selective antagonism of cJun for cancer therapy. J. Exp. Clin. Cancer Res.,  2020, 39(1), 184.
 [http://dx.doi.org/10.1186/s13046-020-01686-9] [PMID: 32917236]

[131]
Fan, F.; Podar, K. The role of AP-1 transcription factors in plasma cell biology and multiple myeloma pathophysiology. Cancers (Basel),  2021, 13(10), 2326.
 [http://dx.doi.org/10.3390/cancers13102326] [PMID: 34066181]

[132]
Wan, P.; Zhang, S.; Ruan, Z.; Liu, X.; Yang, G.; Jia, Y.; Li, Y.; Pan, P.; Wang, W.; Li, G.; Chen, X.; Liu, Z.; Zhang, Q.; Luo, Z.; Wu, J. AP-1 signaling pathway promotes pro-IL-1β transcription to facilitate NLRP3 inflammasome activation upon influenza A virus infection. Virulence,  2022, 13(1), 502-513.
 [http://dx.doi.org/10.1080/21505594.2022.2040188] [PMID: 35300578]

[133]
Zhou, L.; Xue, C.; Chen, Z.; Jiang, W.; He, S.; Zhang, X. c-Fos is a mechanosensor that regulates inflammatory responses and lung barrier dysfunction during ventilator-induced acute lung injury. BMC Pulm. Med.,  2022, 22(1), 9.
 [http://dx.doi.org/10.1186/s12890-021-01801-2] [PMID: 34986829]
Rights & Permissions Print Cite
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/0929867330666230209100059	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

Activating Protein-1 (AP-1): A Promising Target for the Treatment of Fibrotic Diseases

Abstract Play Pause

Related Journals

Related Books

Abstract
