{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T02:53:09Z","timestamp":1773802389513,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,11,19]],"date-time":"2018-11-19T00:00:00Z","timestamp":1542585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81473215"],"award-info":[{"award-number":["81473215"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Myofibroblast apoptosis is essential for normal resolution of wound repair, including cardiac infarction repair. Impaired cardiac myofibroblast (CMF) apoptosis is associated with excessive extracellular matrix (ECM) deposition, which could be responsible for pathological cardiac fibrosis. Conventionally, angiotensin II (Ang II), a soluble peptide, is implicated in fibrogenesis because it induces cardiac fibroblast (CFb) proliferation, differentiation, and collagen synthesis. However, the role of Ang II in regulation of CMF survival and apoptosis has not been fully clarified. In this report, we cultured neonatal rat CFbs, which transform into CMFs after passage 3 (6\u20138 days), and investigated the effects of Ang II on CMFs challenged by TNF\u2010\u03b1 combined with cycloheximide and the underlying mechanisms. Here, we show that Ang II rapidly activates MAPKs but not AKT in CMFs and confers apoptosis resistance, as evidenced by the inhibition of caspase\u20103 cleavage, early apoptotic cells and late apoptotic cells. This inhibitory effect of Ang II was reversed by blockade of AT1 or inactivation of ERK1\/2 or RSK1 but not AT2, indicating that activation of the prosurvival AT1\/ERK1\/2\/RSK1 signaling pathway mediates apoptosis resistance. TGF\u2010\u03b2, a latent fibrotic factor, was found to have no relation to Ang II\u2010induced apoptosis resistance in our study. Furthermore, Ang II\u2010mediated apoptosis resistance, which was conferred by activation of the AT1\/ERK1\/2\/RSK1 signaling pathway, was also confirmed in human adult ventricular cardiac myofibroblasts. Collectively, our findings suggest a novel profibrotic mechanism of Ang II in which it promotes myofibroblast resistance to apoptosis in addition to classical mechanisms, providing a potential novel therapeutic approach by targeting prosurvival signaling pathways. \u00a9 2018 IUBMB Life, 71(1):261\u2013276, 2019<\/jats:p>","DOI":"10.1002\/iub.1967","type":"journal-article","created":{"date-parts":[[2018,11,19]],"date-time":"2018-11-19T15:51:22Z","timestamp":1542642682000},"page":"261-276","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Angiotensin II confers resistance to apoptosis in cardiac myofibroblasts through the AT1\/ERK1\/2\/RSK1 pathway"],"prefix":"10.1002","volume":"71","author":[{"given":"Wenfeng","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College  Shantou Guangdong China"},{"name":"Pharmaceutical Laboratory, The First Affiliated Hospital Shantou University Medical College  Shantou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuping","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuchun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Pharmaceutical Laboratory, The First Affiliated Hospital Shantou University Medical College  Shantou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College  Shantou Guangdong China"},{"name":"Pharmaceutical Laboratory, The First Affiliated Hospital Shantou University Medical College  Shantou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenfei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College  Shantou Guangdong China"},{"name":"Pharmaceutical Laboratory, The First Affiliated Hospital Shantou University Medical College  Shantou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongquan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, The First Affiliated Hospital Shantou University Medical College  Shantou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangna","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, The First Affiliated Hospital Shantou University Medical College  Shantou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhong","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, The First Affiliated Hospital Shantou University Medical College  Shantou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danmei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College  Shantou Guangdong China"},{"name":"Pharmaceutical Laboratory, The First Affiliated Hospital Shantou University Medical College  Shantou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6856-1192","authenticated-orcid":false,"given":"Ganggang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shantou University Medical College  Shantou Guangdong China"},{"name":"Pharmaceutical Laboratory, The First Affiliated Hospital Shantou University Medical College  Shantou Guangdong China"},{"name":"Department of Cardiovascular Diseases, The First Affiliated Hospital Shantou University Medical College  Shantou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.243162"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-5930-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399411001967"},{"key":"e_1_2_8_5_1","first-page":"868","article-title":"The alpha\u2010smooth muscle actin\u2010positive cells in healing human myocardial scars","volume":"145","author":"Willems I. E.","year":"1994","journal-title":"Am. J. Pathol."},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2004.23602.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404616200"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00036.2005"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00044-4"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568006033337276"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.96.11.4065"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11936-011-0126-9"},{"key":"e_1_2_8_13_1","first-page":"10","article-title":"Renin\u2010angiotensin\u2010aldosterone signaling inhibitors\u2010losartan, Enalapril, and Cardosten\u2010prevent infarction\u2010induced heart failure development in rats","volume":"22","author":"Kiss K.","year":"2016","journal-title":"Altern. Ther. Health Med."},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2001.1365"},{"key":"e_1_2_8_15_1","first-page":"273","article-title":"Regulation of apoptosis by angiotensin II in the heart and lungs (review)","volume":"7","author":"Filippatos G.","year":"2001","journal-title":"Int. J. Mol. Med."},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119452"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7290198"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00370-1"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01139.2002"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000141528.54850.bd"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c150006"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.07.015"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12351"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0447OC"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.12.021"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00287.2006"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-1536-6-5"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22322"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162488599"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2013.11.015"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.9.4219"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22280"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e3182137e17"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm809"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700613"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.08.023"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25726"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5288.782"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5288.787"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010384200"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.28.1.91"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e318181fadd"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540600957438"},{"key":"e_1_2_8_44_1","first-page":"959","article-title":"Opposing role of JNK\u2010p38 kinase and ERK1\/2 in hydrogen peroxide\u2010induced oxidative damage of human trophoblast\u2010like JEG\u20103 cells","volume":"7","author":"Tang C.","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02470"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5240.1326"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0817fje"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031771"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2011.01.001"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20110289"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2509"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00310-9"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1349-6"}],"container-title":["IUBMB Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fiub.1967","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iub.1967","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T12:18:43Z","timestamp":1694693923000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/iub.1967"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,19]]},"references-count":52,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1002\/iub.1967"],"URL":"https:\/\/doi.org\/10.1002\/iub.1967","archive":["Portico"],"relation":{},"ISSN":["1521-6543","1521-6551"],"issn-type":[{"value":"1521-6543","type":"print"},{"value":"1521-6551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,19]]},"assertion":[{"value":"2018-08-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}