Inhibitory Effect of Bone Morphogenetic Protein 4 in Retinal Pigment Epithelial-Mesenchymal Transition.
Inhibitory Effect of Bone Morphogenetic Protein 4 in Retinal Pigment Epithelial-Mesenchymal Transition.
复制标题
骨形态发生蛋白4对视网膜色素上皮-间质转化的抑制作用
DOI：
10.1038/srep32182
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发表时间：
2016-09-02
影响因子：
4.6
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Yao H;Li H;Yang S;Li M;Zhao C;Zhang J;Xu G;Wang F
增殖性玻璃体视网膜病变（PVR）是视网膜脱离（RD）的一种严重的视力威胁并发症，其特征是收缩性纤维化膜的形成，其中视网膜色素上皮（RPE）的上皮-间质转化（EMT）是主要事件。最近的研究表明骨形态发生蛋白4 （bone morphogenetic protein 4, BMP4）在抑制纤维化中起重要作用。在本研究中，我们旨在探讨BMP4在PVR病理过程中的作用，特别是在RPE细胞的EMT中。我们发现BMP4及其受体在PVR膜内与细胞角蛋白和α-SMA阳性细胞共标记。此外，在TGF-β诱导的原代RPE细胞EMT过程中，BMP4 mRNA和蛋白表达水平降低，而BMP4受体ALK2、ALK3和ALK6表达水平升高。外源BMP4在RPE细胞mRNA和蛋白水平上抑制TGF-β诱导的上皮标志物下调和间充质标志物上调。此外，BMP4处理可减弱TGF-β诱导的凝胶收缩、细胞迁移和Smad2/3磷酸化。然而，内源性BMP4的敲低刺激了EMT标记物的变化。我们的研究结果证实了BMP4可能通过Smad2/3途径抑制TGF-β介导的RPE细胞EMT并抑制收缩的假设。这可能是一种治疗PVR的潜在方法。
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.
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影响因子：
7.3
作者：
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通讯作者：
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影响因子：
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