title: Resveratrol inhibits high glucose induced collagen upregulation in cardiac fibroblasts through regulating TGF-β1-Smad3 signaling pathway.
abstract: Cardiac fibrosis is a common pathological process presented in a variety of diseases, including hypertension and diabetes. Cardiac fibroblasts (CFs) have been identified as the most important participants in the development of cardiac fibrosis. Exposure of cultured CFs to high glucose (HG) or angiotensin II (Ang II) resulted in increased collagen synthesis. Resveratrol (Res) is a natural polyphenol exhibiting anti-fibrosis effects in a number of different organs fibrosis process, whether Res can prevent HG and Ang II induced fibrosis response in CFs remains unclear. The aim of this work was to evaluate the effects of Res in HG and Ang II induced fibrosis response in CFs. We cultured rat CFs in either normal glucose (5.6 mM) or HG (25 mM) media in the presence of Res or not and the changes in collagens synthesis and TGF-β1 production were assessed by Real-time PCR, Western blotting, and enzyme linked immunosorbent assay (ELISA). Furthermore, normal and diabetic mice (induced by single dose of streptozotocin (100 mg/kg) via tail vein) receiving Res (10 mg/kg) were used to explore the effects of Res on cardiac fibrosis in vivo. Masson staining and immunohistochemistry were performed to visualize cardiac collagen deposition. Results indicate that CFs exposed to HG condition shows enhanced proliferation rate. Furthermore, in the presence of HG or Ang II, CFs exhibited increased collagens synthesis and TGF-β1 production. And these effects were abolished by Res intervention. In vivo results show that diabetic mice exhibit increased collagen deposition in the cardiac compared with the normal mice. And this change was prevented by the treatment of Res. These results suggest that Res possesses a potential antifibrogenic effect in hypertension and diabetes-related cardiac fibrosis. Moreover, the action mechanism is probably associated with its ability to reduce TGF-β1 content in CFs.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, 277 West Yanta Road, Xi'an 710061, Shaanxi, China; Department of Clinical Laboratory, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, 277 West Yanta Road, Xi'an 710061, Shaanxi, China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, 277 West Yanta Road, Xi'an 710061, Shaanxi, China.
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Zhuo
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, 277 West Yanta Road, Xi'an 710061, Shaanxi, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, 277 West Yanta Road, Xi'an 710061, Shaanxi, China.
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Wan
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, 277 West Yanta Road, Xi'an 710061, Shaanxi, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, 277 West Yanta Road, Xi'an 710061, Shaanxi, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, 277 West Yanta Road, Xi'an 710061, Shaanxi, China. Electronic address: zuyiyuan@mail.xjtu.edu.cn.
authors.forename: Zuyi
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, 277 West Yanta Road, Xi'an 710061, Shaanxi, China. Electronic address: imyuewu@gmail.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D051900:Smad3 Protein / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051900:Smad3 Protein; D013267:Stilbenes; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D003094:Collagen; D005947:Glucose; D000077185:Resveratrol
keywords: Angiotensin II (Ang II); Cardiac fibroblasts (CFs); Cardiac fibrosis; Collagens; Resveratrol (Res)