title: Knockdown of eIF3a ameliorates cardiac fibrosis by inhibiting the TGF-β1/Smad3 signaling pathway.
abstract: Cardiac fibroblasts are key effector cells in the pathogenesis of cardiac fibrosis. The eukaryotic translation initiation factor (eIF) 3a is the largest subunit of the eIF3 complex and has been involved in renal fibrosis. However, the precise role of eIF3a in myofibroblast differentiation and cardiac fibrosis remains unknown. Accordingly, in our present study, we tested the expression of eIF3a in transforming growth factor β1 (TGF-β1)-induced rat CFs and found that eIF3a was upregulated in TGF-β1-induced rat CFs. Then the role and mechanism of eIF3a in cardiac fibrosis were explored. Our results found that the eIF3a expression was significantly up-regulated in TGF-β1-induced CFs. Knockdown of eIF3a significantly inhibited TGF-β1-induced CF proliferation, as well as suppressed the expression levels of α-smooth muscle actin (α-SMA) and SM22α. Mechanistically, knockdown of eIF3a attenuated TGF-β1-induced Smad3 activation in CFs. In summary, our present study firstly demonstrated that silencing eIF3a might alleviate TGF-β1-induced cardiac fibrogenesis in CFs by inhibiting Smad3 activation, and suggest that eIF3a may be positioned as a new and promising target for the prevention and treatment of cardiac fibrosis.
authors.affiliation: Henan Provincial People's Hospital Department of Emergency Zhengzhou China.
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.affiliation: Zhengzhou First People's Hospital Department of Endocrinology Zhengzhou China.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: Henan Provincial People's Hospital Department of Emergency Zhengzhou China.
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.affiliation: Henan Provincial People's Hospital Department of Emergency Zhengzhou China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Henan Provincial People's Hospital Department of Emergency Zhengzhou China.
authors.forename: L
authors.initials: L
authors.lastname: Qin
authors.affiliation: Henan Provincial People's Hospital Department of Emergency Zhengzhou China yingjiehn@163.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Chu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism*; D005355:Fibrosis; D055785:Gene Knockdown Techniques; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D039621:Eukaryotic Initiation Factor-3; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1