Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1983355 | The International Journal of Biochemistry & Cell Biology | 2016 | 12 Pages |
Abstract
MicroRNAs (miRNAs) are important for the proliferation of endothelial cells and have been shown to be involved in diabetic retinopathy (DR). In previous study, we found that miRNAs might play a critical role in hyperglycemia-induced endothelial cell proliferation based on miRNA expression profiling. Here, the roles of microRNA-18b (miR-18b) in the proliferation of human retinal endothelial cells (HRECs) were investigated in an in vitro model of HRECs grown in high glucose. We identified that levels of miR-18b were decreased in high-glucose-induced HRECs, compared with those in cells incubated in normal glucose. However, the reduction of miR-18b up-regulated vascular endothelial growth factor (VEGF) secretion and promoted effects on in vitro proliferation of HRECs. Mechanistically, insulin growth factor-1 (IGF-1) was identified as a target of miR-18b. IGF-1 simulation could antagonize the effect induced by miR-18b up-regulation, promoting cell proliferation and increasing VEGF production. In contrast, the opposite results were observed with silencing IGF-1, which was consistent with the effects of miR-18b overexpression. MiR-18b exerted its function on VEGF synthesis and cell proliferation by suppressing the IGF-1/insulin growth factor-1 receptor (IGF1R) pathway, consequently inhibiting the downstream phosphorylation of Akt, MEK, and ERK. Hence, this may provide a new insight into understanding the mechanism of DR pathogenesis, as well as a potential therapeutic target for proliferative DR.
Keywords
PI3KHRECsPDRIGF1RIGF-1recKi67miRNAs3′untranslated region3′UTRMAPKv-akt murine thymoma viral oncogene homologAktdiabetic retinopathyProliferative diabetic retinopathymicroRNAsHuman retinal endothelial cellsInsulin growth factor 1Insulin growth factor-1Vascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)phosphatidylinositol 3 kinasemitogen-activated protein kinasehigh glucose
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Authors
Jin-hui Wu, Yi-han Wang, Wei Wang, Wei Shen, Yan-zhi Sang, Lin Liu, Cui-min Chen,