title: Resveratrol inhibits transforming growth factor-β2-induced epithelial-to-mesenchymal transition in human retinal pigment epithelial cells by suppressing the Smad pathway.
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.
authors.affiliation: Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan; Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ching-Long
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan; Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yi-Hao
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Tai
authors.affiliation: Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Liang
authors.affiliation: Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan; Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Da-Wen
authors.initials: DW
authors.lastname: Lu
authors.affiliation: Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan; Department of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Jiann-Torng
authors.initials: JT
authors.lastname: Chen
mesh_terms: D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D000077185:Resveratrol; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D053781:Transforming Growth Factor beta2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D013267:Stilbenes; D053781:Transforming Growth Factor beta2; D000077185:Resveratrol
keywords: epithelial-to-mesenchymal transition; proliferative vitreoretinopathy; resveratrol; retinal pigment epithelial cells; transforming growth factor-β2