ABSTRACT

High-mobility group AT-hook2 (HMGA2), serving as an architectural transcription factor, participates in plenty of biological processes. Our study is aimed at illustrating the effect of HMGA2 on hypoxia-induced HUVEC injury and the underlying mechanism. To induce hypoxia-related cell injury, HUVECs were exposed to hypoxic condition for 12–24 h. Molecular expression was determined by Western blot analysis, real-time PCR and immunofluorescence staining. Cell migration was monitored by wound healing assay and Transwell chamber assay. Cell proliferation and apoptosis were measured by MTT assay kits and TUNEL staining. In this study, we discovered that HMGA2 was upregulated in hypoxia-induced HUVECs. Overexpression of HMGA2 promoted cell migration, decreased the apoptosis ratio in response to hypoxia stimulation, while HMGA2 knockdown inhibited cell migration and accelerated apoptosis in HUVECs under hypoxic condition. Mechanistically, we found that HMGA2 induced increased expression of HIF-1α,VEGF, eNOS and AKT. eNOS knockdown significantly reduced HMGA2-mediated pro-migration effects, and AKT knockdown strikingly counteracted HMGA2-mediated anti-apoptotic effect. Hence, our data indicated that HMGA2 promoted cell migration by regulating HIF-1α/VGEF/eNOS signaling and prevented cell apoptosis by activating HIF-1α/VGEF/AKT signaling in HUVECs.

摘要

高迁移率群 AT-hook2 (HMGA2) 作为一种结构转录因子，参与了大量的生物过程。我们的研究旨在说明 HMGA2 对缺氧诱导的 HUVEC 损伤的影响及其潜在机制。为了诱导缺氧相关的细胞损伤，将 HUVEC 暴露在缺氧条件下 12-24 小时。通过蛋白质印迹分析、实时PCR和免疫荧光染色确定分子表达。通过伤口愈合试验和 Transwell 室试验监测细胞迁移。通过MTT测定试剂盒和TUNEL染色测量细胞增殖和凋亡。在这项研究中，我们发现 HMGA2 在缺氧诱导的 HUVEC 中上调。HMGA2 的过表达促进细胞迁移，降低响应缺氧刺激的细胞凋亡率，而 HMGA2 敲低抑制细胞迁移并加速缺氧条件下 HUVEC 的凋亡。从机制上讲，我们发现 HMGA2 诱导 HIF-1α、VEGF、eNOS 和 AKT 的表达增加。eNOS 组合式显着降低了 HMGA2 介导的促迁移作用，而 AKT 组合式显着抵消了 HMGA2 介导的抗凋亡作用。因此，我们的数据表明 HMGA2 通过调节 HIF-1α/VGEF/eNOS 信号传导促进细胞迁移，并通过激活 HUVEC 中的 HIF-1α/VGEF/AKT 信号传导阻止细胞凋亡。