title: Ets-1 upregulation mediates angiotensin II-related cardiac fibrosis.
abstract: Ets-1, the prototypical member of the family of Ets transcription factors, has been shown to participate in tissue fibrotic remodeling. However, its role in cardiac fibrosis has not been established. The aim of this study was to investigate the role of Ets-1 in profibrotic actions of angiotensin II (Ang II) in cardiac fibroblasts (CFs) and in the in vivo heart. In growth-arrested CFs, Ang II induced Ets-1 expression in a time- and concentration-dependent manner. Pretreatment with Ang II type 1 receptor blocker losartan, protein kinase C inhibitor bisindolylmaleimide I, extracellular signal-regulated kinase (ERK) inhibitor PD98059, or c-Jun NH(2)-terminal kinase (JNK) inhibitor SP600125 partly inhibited this induction accompanied with impaired cell proliferation and production of plasminogen activator inhibitor-1 (PAI-1) and connective tissue growth factor (CTGF) protein, the two downstream targets of Ets-1. Knockdown of Ets-1 by siRNA significantly inhibited the inductive effects of Ang II on cell proliferation and expression of CTGF and PAI-1. Moreover, the levels of Ets-1, PAI-1 and CTGF protein were simultaneously upregulated in left ventricle of Ang II-infused rats in parallel with an increase in the activation of ERK and JNK. Our data suggest that Ets-1 may mediate Ang II-induced cardiac fibrotic effects.
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine Xi'an, Shaanxi 710004, China.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Hao
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine Xi'an, Shaanxi 710004, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine Xi'an, Shaanxi 710004, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine Xi'an, Shaanxi 710004, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine Xi'an, Shaanxi 710004, China.
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Gao
authors.affiliation: Institute of Cardiovascular Science, Peking University Health Science Center Beijing 100191, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Science, Peking University Health Science Center Beijing 100191, China.
authors.forename: Nanping
authors.initials: N
authors.lastname: Wang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology*; D006321:Heart / Q000187:drug effects; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C494043:Ets1 protein, rat; D017395:Plasminogen Activator Inhibitor 1; D050784:Proto-Oncogene Protein c-ets-1; D000804:Angiotensin II; D055513:Connective Tissue Growth Factor; D003094:Collagen; D019808:Losartan
keywords: Angiotensin; Ets-1; fibroblast; fibrosis