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Haipei Yao, Shuai Yang, Hui Li, Min Li, Fang Wang; Bone morphogenetic protein 4 inhibits transforming growth factor-β1-induced epithelial-mesenchymal transition in retinal pigment epithelial cells. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5371.
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© ARVO (1962-2015); The Authors (2016-present)
Proliferative vitreoretinopathy (PVR), a major complication of retinal detachment (RD), is characterized by the formation of fibrotic membranes that contains transdifferentiated retinal pigment epithelial (RPE) cells. These processes, regulated by various growth factors, are extensively studied to hope to interfere and to suppress the transdifferentiated RPE and disordered cytokines in vitreous. Recent data suggest an important role of bone morphogenic protein 4 (BMP4) in the suppression of fibrosis. The present study is to investigate the role of BMP4 in the process of epithelial-mesenchymal transition (EMT) of RPE.
BMP4 and its receptors Activin-like kinase (ALK) 2, ALK3, ALK6 expression were examined on surgical PVR membranes by using immunofluorescence. Primary RPE cells isolated from human donors and RPE cell line ARPE-19 were cultured and treated with and without TGF-β1 and BMP4. Further more, the mRNA and protein expression of BMP4 and its receptors, the epithelial markers E-cadherin, zona occludens (ZO)-1 and the mesenchymal markers α-smooth muscle actin (SMA), fibronectin (FN) and vimentin were examined via RT-real time quantitative PCR, Western blot analysis and Immunofluorescence. Scratch assay and modified Boyden chamber assay were performed to assess the migration of the cells. Western blot were performed to analyze the signaling proteins. Two-tailed Student’s t-test was used for statistical analysis.
BMP4 and its receptors were expressed on the PVR membrane. The mRNA and protein expression of BMP4 was decreased (0.603 fold of control, p=0.001) and its receptors ALK2, ALK3, ALK6 were increased by 2.162 fold (p=0.0004), 2.363 fold (p=0.0001) and 2.145 fold (p=0.0083) respectively in the process of TGF-β1-induced EMT in primary RPE and ARPE-19. BMP4 inhibits TGF-β1-induced epithelial markers downregulation, mesenchymal markers upregulation and migration in primary RPE and ARPE-19. Additionally, BMP4 treatment attenuates TGF-β1-induced Smad2/3 phosphorylation.
Our result confirmed the hypothesis that BMP4 might inhibit EMT mediated by TGF-β1 in RPE cells via Smad2/3 pathway, and it might be a potential treatment to PVR.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
BMP4 and its receptors are expressed on PVR membranes, and the expression of BMP4 decreased and receptors increased in RPE in TGF-β1 treatment.
BMP4 inhibits TGF-β1-induced EMT in RPE cells.
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