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H. Lee, S. O'Meara, C. O'Brien, R. Kane; The Role of Gremlin, a BMP Antagonist, and Epithelial to Mesenchymal Transition in Proliferative Vitreoretinopathy. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5723.
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© ARVO (1962-2015); The Authors (2016-present)
Proliferative vitreoretinopathy (PVR) is a major reason for failure of retinal detachment surgery, characterized by the formation of scar-like tissue, which contains transdifferentiated retinal pigment epithelial (RPE) cells. The scar tissue occurs in response to growth factors such as transforming growth factor-beta (TGF-ß) and epidermal growth factor (EGF). We postulate that transdifferentiation of RPE cells may arise via epithelial to mesenchymal transition (EMT). Bone morphogenetic proteins (BMPs) are expressed in the retina and have an antiproliferative role. Gremlin is expressed in the posterior segment of the eye and is a BMP antagonist. We aim to establish a model of PVR by inducing EMT in the human RPE cell line ARPE-19 using TGF-ß and EGF, and to establish the contribution of Gremlin to EMT.
ARPE-19 cells were cultured and stimulated with TGF-ß1, EGF and Gremlin. The expression of α-smooth muscle actin (α-SMA), vimentin and zona occludens (ZO-1) were examined via PCR, western blotting and immunofluorescence. Zymography was performed for matrix metalloproteinase (MMP) activity. Scratch assays were performed to assess migration.
A model of EMT was established in the ARPE-19 cell line using TGF-ß1 and EGF. The characteristics of EMT include; gain of α-SMA, loss of ZO-1, upregulation of MMP activity and enhanced migration. Gremlin plays an important role in this process, contributing to the gain of α-SMA, loss of ZO-1 and the upregulation of MMP activity.
EMT occurs in vitro in the ARPE-19 cell line in response to the growth factors TGF-ß1 and EGF and is also induced by the BMP antagonist Gremlin.
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