Overexpression of Axl reverses endothelial cells dysfunction in high glucose and hypoxia
Overexpression of Axl reverses endothelial cells dysfunction in high glucose and hypoxia
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DOI：
10.1002/jcb.28462
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发表时间：
2019-07
影响因子：
4
通讯作者：
Zuo Pei-Yuan;Liu Yu-wei;Zhao Xiang-nan;Tong Song;Zhang Rong;He Xiao-xiao;Shan Sheng-Shuai;Wang Kun;Liu Cheng-yun
中科院分区：
文献类型：
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作者：
Zuo Pei-Yuan;Liu Yu-wei;Zhao Xiang-nan;Tong Song;Zhang Rong;He Xiao-xiao;Shan Sheng-Shuai;Wang Kun;Liu Cheng-yun
受体酪氨酸激酶Axl参与糖尿病血管疾病。本研究旨在探讨高糖对体外培养的内皮细胞缺氧损伤及Axl表达的影响，并探讨Axl过表达对高糖损伤的保护机制。结果表明，高糖可抑制缺氧条件下人脐静脉内皮细胞（HUVECs）和EAhy 926细胞的血管生成。此外，高糖抑制缺氧条件下Axl和缺氧诱导因子1-α（HIF-1α）蛋白的表达。Axl过表达可显著逆转高糖/缺氧条件下内皮细胞功能障碍。此外，Axl过表达可通过PI 3 K/Akt/mTOR/p70 S6 K信号通路而非Mek/Erk途径增加高糖/缺氧条件下EAhy 926细胞中HIF-1α蛋白的合成。这项研究表明，高糖可以改变缺氧条件下Axl信号和HIF-1α。Axl的过表达可能通过其下游信号在高糖/缺氧条件下挽救内皮细胞功能障碍和HIF-1α的表达。
The receptor tyrosine kinase Axl is involved in diabetic vascular disease. This study aims to investigate the effect of high glucose on endothelial cells injury and Axl expression in hypoxia condition in vitro, and we present details of the mechanism associated with overexpression of Axl rescue the high glucose injury. Our results showed that high glucose impaired both human umbilical vein endothelial cells (HUVECs) and EAhy926 cells angiogenesis in hypoxia condition. In addition, high glucose inhibits Axl and hypoxia‐inducible factor 1‐α (HIF‐1α) protein expression in hypoxia condition. Axl overexpression significantly reversed endothelial cells dysfunction in high glucose/hypoxia. Furthermore, Axl overexpression in EAhy926 cells increases HIF‐1α protein synthesis through PI3K/Akt/mTOR/p70 S6K signal pathway but not Mek/Erk in high glucose/hypoxia condition. This study demonstrates that high glucose can alter Axl signaling and HIF‐1α in hypoxia condition. Overexpression of Axl may rescue endothelial cells dysfunction and HIF‐1α expression through its downstream signals in high glucose/hypoxia.