Resveratrol inhibits TGF-β1-induced fibrotic effects in human fibroblasts

被引:4
作者
Fan, Jianwu [1 ,3 ]
Wei, Shuang [4 ]
Zhang, Xiaoyan [2 ]
Chen, Li [1 ]
Zhang, Xin [1 ]
Jiang, Yaping [1 ]
Sheng, Minjie [4 ]
Chen, Yihui [1 ]
机构
[1] Tongji Univ, Yangpu Hosp, Sch Med, Dept Ophthalmol, Shanghai 200090, Peoples R China
[2] Fudan Univ, Huashan Hosp, Dept Ophthalmol, Shanghai 200040, Peoples R China
[3] Tongji Univ, Yangpu Hosp, Ctr Clin Res & Translat Med, Sch Med, Shanghai 200090, Peoples R China
[4] Tongji Univ, Yangzhi Rehabil Hosp, Sch Med, Dept Ophthalmol, Shanghai 201600, Peoples R China
基金
中国国家自然科学基金;
关键词
Resveratrol; Pterygium; Fibrosis; TGF-f31; Smad3; AKT; p38; MAPK; CULTURED PTERYGIUM FIBROBLASTS; FIBROSIS; ACTIVATION; CELLS; BETA;
D O I
10.1265/ehpm.23-00020
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
Background: Resveratrol is a polyphenolic phytoalexin which has the properties of anti-oxidant, anti-inflammatory and anti -fibrotic effects. The aim of this study was to investigate the anti -fibrotic effects of resveratrol in primary human pterygium fibroblasts (HPFs) and elucidate the underlying mechanisms.Method: Profibrotic activation was induced by transforming growth factor-beta1 (TGF-f31). The expression of profibrotic markers, including type 1 collagen (COL1), a-smooth muscle actin (a-SMA), and fibronectin, were detected by western blot and quantitative real-time-PCR after treatment with various concentrations of resveratrol in HPFs to investigate the anti-fibrotic effects. Relative signaling pathways downstream of TGF-f31 were detected by Western blot to assess the underlying mechanism. Cell viability and apoptosis were assessed using CCK-8 assay and flow cytometry to evaluate proliferation and drug-induced cytotoxicity. Cell migration and contractile phenotype were detected through wound healing assay and collagen gel contraction assay.Results: The expression of a-SMA, FN and COL1 induced by TGF-f31 were suppressed by treatment with resveratrol in dose -dependent manner. The Smad3, mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol-3-kinase (PI3K) / protein kinase B (AKT) pathways were activated by TGF-f31, while resveratrol attenuated those pathways. Resveratrol also inhibited cellular proliferation, migration and contractile phenotype, and induced apoptosis in HPFs. Conclusions: Resveratrol inhibit TGF-f31-induced myofibroblast activation and extra cellular matrix synthesis in HPFs, at least partly, by regulating the TGF-f3/Smad3, p38 MAPK and PI3K/AKT pathways.
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页数:9
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