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BMC Cardiovascular Disorders
Published in: BMC Cardiovascular Disorders 1/2016

Open Access 01-12-2016 | Research article

Resveratrol ameliorates myocardial fibrosis by inhibiting ROS/ERK/TGF-β/periostin pathway in STZ-induced diabetic mice

Authors: Han Wu, Guan-Nan Li, Jun Xie, Ran Li, Qin-Hua Chen, Jian-Zhou Chen, Zhong-Hai Wei, Li-Na Kang, Biao Xu

Published in: BMC Cardiovascular Disorders | Issue 1/2016

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Abstract

Background

Myocardial fibrosis is an essential hallmark of diabetic cardiomyopathy (DCM) contributing to cardiac dysfunctions. Resveratrol, an antioxidant, exerts its anti-fibrotic effect via inhibition of oxidative stress, while the underlying molecular mechanism remains largely elusive. Periostin, a fibrogenesis matricellular protein, has been shown to be associated with oxidative stress. In the present study, we investigated the role of periostin in anti-fibrotic effect of resveratrol in streptozocin (STZ)-induced diabetic heart and the underlying mechanisms.

Methods

Diabetic mice were induced by STZ injection. After treatment with resveratrol (5 or 25 mg/kg/day i.g) or Saline containing 0.5 % carboxymethyl cellulose (CMC) for 2 months, the hearts were detected for oxidative stress and cardiac fibrosis using western blot, Masson’s trichrome staining and Dihydroethidium (DHE) staining. In in vitro experiments, proliferation and differentiation of fibroblasts under different conditions were investigated through western blot, 3-(4,5)-dimethylthiahiazo (−z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay and immunofluorescence staining.

Results

Administration of resveratrol significantly mitigated oxidative level, interstitial fibrosis and expressions of related proteins in STZ-induced diabetic hearts. In in vitro experiments, resveratrol exhibited anti-proliferative effect on primary mouse cardiac fibroblasts via inhibiting reactive oxygen species (ROS)/extracellular regulated kinase (ERK) pathway and ameliorated myofibroblast differentiation via suppressing ROS/ERK/ transforming growth factor β (TGF-β)/periostin pathway.

Conclusion

Increased ROS production, activation of ERK/TGF-β/periostin pathway and myocardial fibrosis are important events in DCM. Alleviated ROS genesis by resveratrol prevents myocardial fibrosis by regulating periostin related signaling pathway. Thus, inhibition of ROS/periostin may represent a novel approach for resveratrol to reverse fibrosis in DCM.
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Metadata
Title
Resveratrol ameliorates myocardial fibrosis by inhibiting ROS/ERK/TGF-β/periostin pathway in STZ-induced diabetic mice
Authors
Han Wu
Guan-Nan Li
Jun Xie
Ran Li
Qin-Hua Chen
Jian-Zhou Chen
Zhong-Hai Wei
Li-Na Kang
Biao Xu
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2016
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-015-0169-z

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