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


Cite item

Full Text

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.

About the authors

Zixin Pi

Department of Dermatolog, The Second Xiangya Hospital of Central South University

Email: info@benthamscience.net

Xiangning Qiu

Department of Dermatology, The Second Xiangya Hospital of Central South University

Email: info@benthamscience.net

Jiani Liu

Department of Dermatology, The Second Xiangya Hospital of Central South University

Email: info@benthamscience.net

Yaqian Shi

Department of Dermatology,, The Second Xiangya Hospital of Central South University

Email: info@benthamscience.net

Zhuotong Zeng

Department of Dermatology,, The Second Xiangya Hospital of Central South University

Author for correspondence.
Email: info@benthamscience.net

Rong Xiao

Department of Dermatology, The Second Xiangya Hospital of Central South University

Author for correspondence.
Email: info@benthamscience.net

References

  1. Shaulian, E.; Karin, M. AP-1 as a regulator of cell life and death. Nat. Cell Biol., 2002, 4(5), E131-E136. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1016/j.trsl.2019.02.010 PMID: 30876809
  12. Mack, M. Inflammation and fibrosis. Mat Biol., 2018, 68-69, 106-121. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1242/jcs.01589 PMID: 15564374
  17. Chang, L.; Karin, M. Mammalian MAP kinase signalling cascades. Nature, 2001, 410(6824), 37-40. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1002/path.5680 PMID: 33834494
  27. Tzavlaki, K.; Moustakas, A. TGF-β Signaling. Biomolecules, 2020, 10(3), 487. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1172/JCI66028 PMID: 23635787
  70. Hernandez-Gea, V.; Friedman, S.L. Pathogenesis of liver fibrosis. Annu. Rev. Pathol., 2011, 6(1), 425-456. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1002/ejhf.696 PMID: 28157267
  87. Frangogiannis, N.G. Cardiac fibrosis. Cardiovasc. Res., 2021, 117(6), 1450-1488. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1186/s12890-021-01801-2 PMID: 34986829

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers