Downregulation of endothelial microRNA-200b supports cutaneous wound angiogenesis by desilencing GATA binding protein 2 and vascular endothelial growth factor receptor 2.
Downregulation of endothelial microRNA-200b supports cutaneous wound angiogenesis by desilencing GATA binding protein 2 and vascular endothelial growth factor receptor 2.
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内皮 microRNA-200b 的下调通过使 GATA 结合蛋白 2 和血管内皮生长因子受体 2 去沉默来支持皮肤伤口血管生成。
DOI：
10.1161/atvbaha.112.248583
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发表时间：
2012-06
期刊：
影响因子：
--
通讯作者：
Sen CK
中科院分区：
文献类型：
--
作者：
Chan YC;Roy S;Khanna S;Sen CK
MicroRNAs (miRs) regulate angiogenesis by posttranscriptional silencing of target genes. The significance of angiostatic miR-200b in switching on skin wound angiogenesis was tested. Wounding caused imminent and transient downregulation of miR-200b in dermal wound-edge endothelial cells. Derailing this injury response by lentiviral delivery of miR-200b in vivo impaired wound angiogenesis. Computational prediction, target reporter luciferase assay, and Western blot analysis provided first evidence that miR-200b targets globin transcription factor binding protein 2 (GATA2) and vascular endothelial growth factor receptor 2 (VEGFR2). Overexpression of GATA2 or VEGFR2 in endothelial cells rescued the angiostatic effect of miR-200b in vitro. Downregulation of miR-200b derepressed GATA2 and VEGFR2 expression to switch on wound angiogenesis, which was disrupted in diabetic wounds. Treatment of endothelial cells with tumor necrosis factor-α, a proinflammatory cytokine abundant in diabetic wounds, induced miR-200b expression, silenced GATA2 and VEGFR2, and suppressed angiogenesis. These outcomes were attenuated using anti-miR-200b strategy. Neutralization of tumor necrosis factor-α in the diabetic wounds improved wound angiogenesis and closure, which was accompanied by downregulation of miR-200b expression and desilencing of GATA2 and VEGFR2. Injury-induced repression of miR-200b turned on wound angiogenesis. In mice with diabetes mellitus, excessive tumor necrosis factor-α induced miR-200b blunting proangiogenic functions of GATA2 and VEGFR2.
