FGF21 protects human umbilical vein endothelial cells against high glucose-induced apoptosis via PI3K/Akt/Fox3a signaling pathway
FGF21 protects human umbilical vein endothelial cells against high glucose-induced apoptosis via PI3K/Akt/Fox3a signaling pathway
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FGF21通过PI3K/Akt/Fox3a信号通路保护人脐静脉内皮细胞免受高糖诱导的细胞凋亡
DOI：
10.1016/j.jdiacomp.2018.05.012
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发表时间：
2018-08-01
影响因子：
3
通讯作者：
Lin, Xiaolong
中科院分区：
文献类型：
--
作者：
Guo, Dongmin;Xiao, Lele;Lin, Xiaolong
目的：糖尿病大血管病变是糖尿病患者发病和死亡的主要原因。内皮细胞损伤是糖尿病大血管病变的病理前提。成纤维细胞生长因子 21 (FGF21) 是一种关键的代谢调节剂，最近被认为可以保护心肌细胞和血管细胞免受氧化应激引起的体外和体内损伤。本研究旨在探讨FGF21通过磷脂酰肌醇-3-激酶/蛋白激酶B（PI3K/Akt）/FoxO3a途径对人脐静脉内皮细胞（HUVEC）对高糖（HG）诱导的细胞凋亡的保护能力。方法：采用CCK-8法检测细胞活力，通过检测细胞内ROS水平，检测细胞内ROS水平。 DCFH-DA，使用Hoechst 33258核染色和流式细胞术分析（FCA）分析细胞凋亡，通过Western blot检测蛋白质的表达。 结果：结果显示，在暴露于HG之前用FGF21预处理HUVEC可增加细胞活力，同时减少细胞凋亡和活性氧的产生。 Western blot 分析显示 HG 降低 Akt 和 FoxO3a 的磷酸化，并诱导 FoxO3a 的核定位。 FGF21 预处理显着逆转了这种效应。此外，PI3K/Akt 抑制剂 LY294002 阻止了 FGF21 的保护作用。结论：我们的数据表明，FGF21 通过激活 PI3K/Akt/FoxO3a 信号通路来保护 HUVEC 免受 HG 诱导的氧化应激和细胞凋亡。 (C) 2018 Elsevier Inc. 保留所有权利。
Aims: Diabetic macroangiopathy is the main cause of morbidity and mortality in patients with diabetes. Endothelial cell injury is a pathological precondition for diabetic macroangiopathy. Fibroblast growth factor 21 (FGF21) is a key metabolic regulator which has recently been suggested to protect cardiac myocytes and vascular cells against oxidative stress-induced injury in vitro and vivo. In this study, we aimed to investigate the protective capacity of FGF21 in human umbilical vein endothelial cells (HUVECs) against high glucose (HG)-induced apoptosis via phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt)/FoxO3a pathway.Methods: The cell viability was examined by CCK-8 assay, Intracellular ROS levels were measured by the detection of the fluorescent product formed by the oxidation of DCFH-DA, Apoptosis was analyzed using Hoechst 33258 nuclear staining and Flow Cytometry Analysis (FCA), the expression of protein were detected by Western blot.Results: Results show that pretreating HUVECs with FGF21 before exposure to HG increases cell viability, while decreasing apoptosis and the generation of reactive oxygen species. Western blot analysis shows that HG reduces the phosphorylation of Akt and FoxO3a, and induces nuclear localization of FoxO3a. The effects were significantly reversed by FGF21 pre-treatment. Furthermore, the protective effects of FGF21 were prevented by PI3K/Akt inhibitor LY294002.Conclusions: Our data demonstrates that FGF21 protects HUVECs from HG-induced oxidative stress and apoptosis via the activation of PI3K/Akt/FoxO3a signaling pathway. (C) 2018 Elsevier Inc. All rights reserved.