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人视网膜内皮细胞中HIF-1α的稳定调节miRNA和促血管生成生长因子的表达。

Stabilization of HIF-1α in Human Retinal Endothelial Cells Modulates Expression of miRNAs and Proangiogenic Growth Factors.

作者信息

Lazzara Francesca, Trotta Maria Consiglia, Platania Chiara Bianca Maria, D'Amico Michele, Petrillo Francesco, Galdiero Marilena, Gesualdo Carlo, Rossi Settimio, Drago Filippo, Bucolo Claudio

机构信息

Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.

Department of Experimental Medicine, Division of Pharmacology, University of Campania "Luigi Vanvitelli", Naples, Italy.

出版信息

Front Pharmacol. 2020 Jul 17;11:1063. doi: 10.3389/fphar.2020.01063. eCollection 2020.

Abstract

Retinal hypoxia is one of the causative factors of diabetic retinopathy and is also one of the triggers of VEGF release. We hypothesized that specific dysregulated miRNAs in diabetic retinopathy could be linked to hypoxia-induced damage in human retinal endothelial cells (HRECs). We investigated in HRECs the effects of chemical (CoCl) hypoxia on the expression of HIF-1α, VEGF, PlGF, and of a focused set of miRNAs. We found that miR-20a-5p, miR-20b-5p, miR-27a-3p, miR-27b-3p, miR-206-3p, miR-381-3p correlated also with expression of TGFβ signaling pathway genes in HRECs, challenged with chemical hypoxic stimuli. In conclusion, our data suggest that retinal angiogenesis would be promoted, at least under HIF-1α activation, by upregulation of PlGF and other factors such as miRNAs, VEGFA, and TGFβ1.

摘要

视网膜缺氧是糖尿病视网膜病变的致病因素之一,也是血管内皮生长因子(VEGF)释放的触发因素之一。我们推测,糖尿病视网膜病变中特定的失调微小RNA(miRNA)可能与缺氧诱导的人视网膜内皮细胞(HREC)损伤有关。我们研究了化学性(氯化钴)缺氧对HREC中缺氧诱导因子-1α(HIF-1α)、VEGF、胎盘生长因子(PlGF)以及一组特定miRNA表达的影响。我们发现,在受到化学性缺氧刺激的HREC中,miR-20a-5p、miR-20b-5p、miR-27a-3p、miR-27b-3p、miR-206-3p、miR-381-3p也与转化生长因子β(TGFβ)信号通路基因的表达相关。总之,我们的数据表明,至少在HIF-1α激活的情况下,PlGF以及其他因子如miRNA、血管内皮生长因子A(VEGFA)和TGFβ1的上调会促进视网膜血管生成。

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