Glucosamine inhibits epithelial-to-mesenchymal transition and migration of retinal pigment epithelium cells in culture and morphologic changes in a mouse model of proliferative vitreoretinopathy.

To explore the effect of glucosamine (GlcN) on transforming growth factor (TGF)-β signalling and several processes involved in proliferative vitreoretinopathy (PVR). We evaluated the surface levels of TGF-β receptor and its binding of TGF-β in ARPE-19 cells. Release of cytokines and collagen, and expression of signalling intermediates were quantified. Migration was qualitatively and quantitatively examined. The morphology of cells undergoing PVR in vitro and in a mouse PVR model was observed. Glucosamine reduced the surface levels of TGF-β receptor and the ability of ARPE-19 cells to bind TGF-β. In ARPE-19 cells, TGF-β1 plus epidermal growth factor (EGF) or TGF-β2 increased the expression of alpha-smooth muscle actin (α-SMA) and decreased the expression of zona occludens protein (ZO-1). Transforming growth factor-(β2) also caused the release of platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF) and type 1 collagen and increased the phosphorylation of SMAD2 and SMAD3. Platelet-derived growth factor and CTGF stimulated cell migration, and TGF-β2 stimulated wound closure, contraction of collagen and changes in cell morphology. Treatment with GlcN counteracted all of these effects, and its administration in the mouse model reduced the morphologic appearance of PVR. Glucosamine could inhibit the TGF-β signalling pathway in retinal pigment epithelium cells and several of the downstream events associated with epithelial-mesenchymal transition and PVR.

Liang CM ，Tai MC ，Chang YH ，Chen YH ，Chen CL ，Lu DW ，Chen JT ... -  《-》

Inhibition by female sex hormones of collagen gel contraction mediated by retinal pigment epithelial cells.

Kimura K ，Orita T ，Fujitsu Y ，Liu Y ，Wakuta M ，Morishige N ，Suzuki K ，Sonoda KH ... -  《-》

The role of gremlin, a BMP antagonist, and epithelial-to-mesenchymal transition in proliferative vitreoretinopathy.

Lee H ，O'Meara SJ ，O'Brien C ，Kane R ... -  《INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE》

Thrombin induces epithelial-mesenchymal transition and collagen production by retinal pigment epithelial cells via autocrine PDGF-receptor signaling.

Bastiaans J ，van Meurs JC ，van Holten-Neelen C ，Nagtzaam NM ，van Hagen PM ，Chambers RC ，Hooijkaas H ，Dik WA ... -  《-》

Bevacizumab modulates epithelial-to-mesenchymal transition in the retinal pigment epithelial cells via connective tissue growth factor up-regulation.

To investigate the effect of bevacizumab treatment on connective tissue growth factor (CTGF) expression and the induction of epithelial-to-mesenchymal transition in ARPE-19 cells and human donor retinal pigment epithelium (HRPE) cells in vitro. We quantitated the protein and gene expression level of CTGF by ELISA. The effect of Fc-Fc receptor (Fc-FcR) interaction on CTGF expression was evaluated by CD64 siRNA silencing. Expression of epithelial-to-mesenchymal transition markers, alpha-smooth muscle actin (α-SMA) and zona occludens protein (ZO-1) was evaluated by Western blot. Cell migration and collagen gel contraction assay were examined by light microscopy, and collagen production was measured by ELISA. Bevacizumab stimulation increased CTGF expression in ARPE-19 and HRPE cells in a dose-dependent manner. CD64 gene silencing inhibited the effect of bevacizumab-induced CTGF up-regulation. Bevacizumab increased the expression of α-SMA and decreased the expression of ZO-1 in ARPE-19 cells. Bevacizumab also caused the release of type-1 collagen and increased cell migration and contraction of collagen. Bevacizumab exerts pro-fibrotic effects on human RPE cells at clinical doses by up-regulation of CTGF expression via an Fc-FcR interaction. This effect of bevacizumab may be one of the underlying mechanisms involved in age-related macular degeneration therapy or intravitreal bevacizumab-associated complications.

Chen CL ，Liang CM ，Chen YH ，Tai MC ，Lu DW ，Chen JT ... -  《-》