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Hirotaka Yokouchi, Toshiyuki Oshitari, Shuichi Yamamoto; Angiopoietin-like Protein 6 (ANGPTL6) has Angiogenic Activity on Retinal Endothelial Cells under High Glucose Concentrations. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5759.
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© ARVO (1962-2015); The Authors (2016-present)
The progression of diabetic retinopathy is related to an imbalance in the pro- and anti-angiogenic factors in the retina. Because hyperglycemia is a major risk factor for diabetic retinopathy, we hypothesized that angiogenic factors released from RPE cells under high glucose concentrations play a role in the pathogenesis of diabetic retinopathy.
We examined whether tube formation was enhanced in human retinal endothelial (RE) cells cultured in a high glucose medium for ARPE-19 cells. We also investigated whether ANGPTL6 was an angiogenic factor released from ARPE-19 cells under high glucose concentrations, and whether RNA interference (RNAi) molecule against ANGPTL6 affected the enhancement. Finally, we studied whether the cell invasion, cell migration, cell proliferation, and tube formation angiogenic steps were enhanced by recombinant ANGPTL6 protein in cultured human RE cells.
The high glucose conditioned medium enhanced tube formation in the cultured human RE cells. From the results of experiments of using conditioned medium from ARPE-19 cells and RNAi combined for ANGPTL6, we found that ANGPTL6 was one of the angiogenic factors released from ARPE-19 cells under a high glucose concentration. In addition, recombinant ANGPTL6 promoted all of the steps of angiogenesis in human RE cells at a level comparable to that of VEGF in vitro.
We demonstrated that the induction of the angiogenic activity by glucose in ARPE-19 cells is mediated by the up-regulation of ANGPTL6 expression. Our data suggest that RPE cells might contribute to the pathogenesis of diabetic retinopathy by up-regulating the expression of ANGPTL6.
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