title: The critical role of Sestrin 1 in regulating the proliferation of cardiac fibroblasts.
abstract: The proliferation of cardiac fibroblasts is pivotal in the development of cardiac fibrosis. Sestrin 1, which functions as antioxidant, plays diverse roles in the regulation of proliferation and cellular injury that is induced by oxidative stress. However, little is known regarding the impact of Sestrin 1 on the proliferation of cardiac fibroblasts. In the present study, with knockdown of Sestrin 1 by siRNA, we surveyed the effect of Sestrin 1 on cardiac fibroblast proliferation. Downregulation of Sestrin 1 promotes Ang II-induced proliferation of cardiac fibroblasts, leading to increased DNA synthesis and collagen production. Moreover, in the absence of Ang II, a similar phenotype to the basal condition was detected with silencing of Sestrin 1. Further analysis of the pro-proliferating signals revealed that knockdown of Sestrin 1 significantly activated ERK1/2 and mTOR, meanwhile, downregulation of Sestrin 1 also enhanced the expression of collagen type I and CTGF, which play important role in the cardiac fibrosis. Consistent with the antioxidant property of Sestrin 1, we determined that the proliferation induced by silence of Sestrin 1 was accompanied by a remarkably enhanced production of reactive oxygen species (ROS). However, diminishing ROS by NAC, a potent antioxidant, could only partly repress the pro-proliferative effect of Sestrin 1-downregulation. Consequently, our study demonstrated that Sestrin 1 plays an important role in the proliferation of cardiac fibroblasts, and the effect could be partly mediated by decreased oxidative stress.
authors: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China; Department of Cardiology, Jiangmen Central Hospital, Jiangmen 529030, China.
authors: Gang
authors: G
authors: Sun
authors: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.
authors: Ruicong
authors: R
authors: Xue
authors: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.
authors: Fengjuan
authors: F
authors: Yao
authors: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.
authors: Dan
authors: D
authors: Liu
authors: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.
authors: Huiling
authors: H
authors: Huang
authors: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.
authors: Cong
authors: C
authors: Chen
authors: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.
authors: Yanhui
authors: Y
authors: Li
authors: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.
authors: Junyi
authors: J
authors: Zeng
authors: Department of Cardiology, Jiangmen Central Hospital, Jiangmen 529030, China.
authors: Gaoxing
authors: G
authors: Zhang
authors: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China. Electronic address: dongxg@mail.sysu.edu.cn.
authors: Yugang
authors: Y
authors: Dong
authors: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China. Electronic address: liuch75@mail.sysu.edu.cn.
authors: Chen
authors: C
authors: Liu
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D024042:Collagen Type I / Q000096:biosynthesis; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D020868:Gene Silencing; D009206:Myocardium / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000084622:Sestrins
chemical_list: D018797:Cell Cycle Proteins; D024042:Collagen Type I; D055513:Connective Tissue Growth Factor; D017382:Reactive Oxygen Species; C586973:Sesn1 protein, rat; D000084622:Sestrins
keywords: Angiotensin II; Cardiac fibroblasts; Proliferation; Reactive oxygen species; Sestrin 1