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Resveratrol inhibits transforming growth factor-β2-induced epithelial-to-mesenchymal transition in human retinal pigment epithelial cells by suppressing the Smad pathway

Authors Chen CL, Chen YH, Tai MC, Liang CM, Lu DW, Chen JT

Received 5 November 2016

Accepted for publication 16 December 2016

Published 11 January 2017 Volume 2017:11 Pages 163—173

DOI https://doi.org/10.2147/DDDT.S126743

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristian Vilos

Peer reviewer comments 2

Editor who approved publication: Dr Sukesh Voruganti

Ching-Long Chen,1,2 Yi-Hao Chen,1,2 Ming-Cheng Tai,2 Chang-Min Liang,2 Da-Wen Lu,1,2 Jiann-Torng Chen1,2

1Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan; 2Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

Abstract: Proliferative vitreoretinopathy (PVR) is the main cause of failure following retinal detachment surgery. Transforming growth factor (TGF)-β2-induced epithelial-to-mesenchymal transition (EMT) plays an important role in the development of PVR, and EMT inhibition decreases collagen gel contraction and fibrotic membrane formation, resulting in prevention of PVR. Resveratrol is naturally found in red wine and has inhibitory effects on EMT. Resveratrol is widely used in cardioprotection, neuroprotection, chemotherapy, and antiaging therapy. The purpose of this study was to investigate the effects of resveratrol on TGF-β2-induced EMT in ARPE-19 cells in vitro. We found that resveratrol suppressed the decrease of zona occludens-1 (ZO-1) and caused an increase of alpha-smooth muscle actin expression in TGF-β2-treated ARPE-19 cells, assessed using Western blots; moreover, it also suppressed the decrease in ZO-1 and the increase of vimentin expression, observed using immunocytochemistry. Resveratrol attenuated TGF-β2-induced wound closure and cell migration in ARPE-19 cells in a scratch wound test and modified Boyden chamber assay, respectively. We also found that resveratrol reduced collagen gel contraction – assessed by collagen matrix contraction assay – and suppressed the phosphorylation of Smad2 and Smad3 in TGF-β2-treated ARPE-19 cells. These results suggest that resveratrol mediates anti-EMT effects, which could be used in the prevention of PVR.

Keywords: resveratrol, epithelial-to-mesenchymal transition, proliferative vitreoretinopathy, transforming growth factor-β2, retinal pigment epithelial cells

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