title: Role of eukaryotic translation initiation factors 3a in hypoxia-induced right ventricular remodeling of rats.
abstract: OBJECTIVE
  Eukaryotic translation initiation factors 3a (eIF3a) is involved in regulating cell cycle, cell division, growth and differentiation. Previous studies suggest a role of eIF3a on fibrosis disease and cellular proliferation and differentiation of fibroblasts. The present study aims to investigate the role of eIF3a on hypoxia-induced right ventricular (RV) remodeling and underlying mechanism.
  
  
  METHODS
  RV remodeling was induced by hypoxia (10% O2, 3 weeks) in rats. Primary cardiac fibroblasts were cultured in vitro and their proliferation was investigated by MTS and EdU incorporation method. eIF3a knockdown was conducted by eIF3a siRNA. The expression/level of TGF-β1, eIF3a, p27 and α-SMA, collagen-I, collagen-III, ANP and BNP were analyzed by ELISA, real-time PCR or Western blot.
  
  
  RESULTS
  The expression of eIF3a was obviously increased in right ventricle of RV remodeling rats accompanied by up-regulation of α-SMA and collagens. In cultured cardiac fibroblasts, application of exogenous TGF-β1-induced cellular proliferation and differentiation concomitantly with up-regulation of eIF3a expression and down-regulation of p27 expression. The effects of TGF-β1-induced proliferation and up-regulation of α-SMA and collagen in cardiac fibroblasts were abolished by eIF3a siRNA. eIF3a siRNA reversed TGF-β1 induced down-regulation of p27 expression.
  
  
  CONCLUSIONS
  The eIF3a plays a crucial role in hypoxia-induced RV remodeling by regulating TGF-β1-induced proliferation and differentiation of cardiac fibroblasts, which is mediated via eIF3a/p27 pathway.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Wen-Qun
authors.initials: WQ
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Yue-Han
authors.initials: YH
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China; Department of Anatomy, School of Medicine, University of South China, Hengyang 421001, China.
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Wang
authors.affiliation: National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha 410078, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China. Electronic address: yuan_jianli@yahoo.com.
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000235:genetics*; D005347:Fibroblasts; D055785:Gene Knockdown Techniques; D017380:Hypertrophy, Right Ventricular / Q000235:genetics* / Q000473:pathology*; D000860:Hypoxia / Q000473:pathology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: D000199:Actins; D003094:Collagen; D050760:Cyclin-Dependent Kinase Inhibitor p27; D039642:Eukaryotic Initiation Factors; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; C576123:TRIP-1 protein, rat; C498862:Acta2 protein, rat
keywords: Cardiac fibroblasts; Right ventricular remodeling; TGF-β1; eIF3a; p27