title: Inhibitory Effect of Bone Morphogenetic Protein 4 in Retinal Pigment Epithelial-Mesenchymal Transition.
abstract: Proliferative vitreoretinopathy (PVR), a serious vision-threatening complication of retinal detachment (RD), is characterized by the formation of contractile fibrotic membranes, in which epithelial-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is a major event. Recent studies suggest an important role of bone morphogenetic protein 4 (BMP4) in the suppression of fibrosis. In this study, we aimed to investigate the role of BMP4 in the pathological process of PVR, particularly in the EMT of RPE cells. We found that BMP4 and its receptors were co-labelled with cytokeratin and α-SMA positive cells within the PVR membrane. Moreover, the mRNA and protein expression levels of BMP4 were decreased whereas BMP4 receptors ALK2, ALK3 and ALK6 were increased during TGF-β-induced EMT in primary RPE cells. Exogenous BMP4 inhibited TGF-β-induced epithelial marker down-regulation, as well as mesenchymal marker up-regulation at both the mRNA and protein levels in RPE cells. In addition, BMP4 treatment attenuated the TGF-β-induced gel contraction, cell migration and Smad2/3 phosphorylation. However, knockdown of endogenous BMP4 stimulated changes in EMT markers. Our results confirm the hypothesis that BMP4 might inhibit TGF-β-mediated EMT in RPE cells via the Smad2/3 pathway and suppress contraction. This might represent a potential treatment for PVR.
authors: Department of ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.|Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
authors: Haipei
authors: H
authors: Yao
authors: Department of ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
authors: Hui
authors: H
authors: Li
authors: Department of ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.|Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
authors: Shuai
authors: S
authors: Yang
authors: Department of ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
authors: Min
authors: M
authors: Li
authors: Department of ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.
authors: Chun
authors: C
authors: Zhao
authors: Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
authors: Jingfa
authors: J
authors: Zhang
authors: Department of ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.|Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
authors: Guotong
authors: G
authors: Xu
authors: Department of ophthalmology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai, China.|Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
authors: Fang
authors: F
authors: Wang
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000473:pathology*; D051898:Smad1 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism* / Q000473:pathology
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; C497399:SMAD1 protein, human; D051898:Smad1 Protein; D016212:Transforming Growth Factor beta; D003094:Collagen; C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I; C498214:BMPR1B protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I