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Ti zhou, Di Che, Jianxing ma, guoquan Gao; The pathogenic role of Epithelial-mesenchymal transition (EMT) in the fibrosis of diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4244.
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© ARVO (1962-2015); The Authors (2016-present)
Our previous study has shown that fibrosis is an important pathogenic disorder in diabetic retinopathy yet the mechanism is unclear. Recently, it has been reported that epithelial-mesenchymal transition plays a role in the fibrosis in various organs. Therefore, the purpose of this study is to investigate the pathogenic role of EMT in the fibrosis of DR.
Streptozotocin-induced diabetic mice and db/db mice were used as diabetic models. In vitro, cultured retinal pigment epithelial cells were exposed to advanced glycated end products or 30 mM D-glucose. A vector encoding Snail gene and Snail siRNA were transfected into the cells respectively. AKT inhibitor and U0126 were used to block the AKT and ERK activation. The levels of EMT makers, fibrogenic factors, phos-ERK, phos-AKT were determined by immunoblotting and immunostaining.The cell migration was evaluated using transwell assay.
The expression of E-cadherin was reduced, while snail, N-cadherin, Vimentin, β-catenin, α-SMA levels were significantly increased in the diabetic retinas. In vitro, high glucose or AGE elevated snail, N-cadherin, Vimentin, β-catenin and cell migration in ARPE19 cells. Moreover, overexpression of snail elevated the fibronectin and CTGF levels while silencing snail attenuated the over-expression of fibronectin and CTGF induced by high glucose in ARPE19 cells. Mechanically, AKT inhibitor and U0126 significantly reduced the expression of N-cadherin and snail as well as the fibronectin and CTGF levels induced by high glucose.
EMT in the diabetic retina plays a pathogenic role in the fibrosis of diabetic retinopathy and the AKT and ERK signaling pathways regulated the EMT in diabetic retinopathy.Thus,EMT in the retina represents a new pathogenic mechanism and renders a new therapeutic target for fibrosis in DR.
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