BASP1 promotes high glucose-induced endothelial apoptosis in diabetes via activation of EGFR signaling

IF 3.2 3区医学

Journal of Diabetes Investigation Pub Date : 2023-02-08 DOI:10.1111/jdi.13920

Fengnan Sun, Junwei Liu, Yanzheng Wang, Hongmei Yang, Danfeng Song, Haiyan Fu, Xingxing Feng

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引用次数: 2

Abstract

Aims

Diabetes mellitus is a common chronic disease of glucose metabolism. Endothelial dysfunction is an early event in diabetes complicated by cardiovascular disease. This study aimed to reveal the expression of BASP1 and its biological roles in endothelial cell dysfunction in diabetes complicated by cardiovascular disease.

Materials and Methods

By analyzing the databases related to diabetes complicated with coronary heart disease, BASP1 was screened out as an upregulated gene. Human umbilical vein endothelial cells (HUVECs) and primary mouse aortic endothelial cells were treated with high glucose to establish cell models of diabetes-related endothelial dysfunction, and the expression changes of BASP1 were verified by RT-qPCR, western blot, and immunofluorescence. BASP1 was silenced or overexpressed by siRNA or overexpression plasmid, and its effects on cell migration, apoptosis, tube formation, inflammatory response, and ROS were detected. The possible signaling pathway of BASP1 was found and the mechanism of BASP1 on promoting the progression of endothelial dysfunction was explored using the EGFR inhibitor, gefitinib.

Results

Bioinformatics analysis indicated that the expression of BASP1 in patients with diabetes mellitus and concomitant coronary heart disease was increased. High glucose induced the upregulation of BASP1 expression in endothelial cells, and showed a time-dependent relationship. Silencing of BASP1 alleviated the damage of high glucose to endothelial cells. BASP1 regulated EGFR positively. The promoting effect of BASP1 on endothelial cell apoptosis may be achieved by regulating the EGFR pathway.

Conclusion

BASP1 promotes endothelial cell injury induced by high glucose in patients with diabetes, which may be activated by activating the EGFR pathway.

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BASP1通过激活EGFR信号通路促进高糖诱导的糖尿病内皮细胞凋亡

目的糖尿病是一种常见的慢性糖代谢疾病。内皮功能障碍是糖尿病合并心血管疾病的早期事件。本研究旨在揭示BASP1的表达及其在糖尿病合并心血管疾病内皮细胞功能障碍中的生物学作用。材料与方法通过分析糖尿病合并冠心病相关数据库，筛选出上调基因BASP1。采用高糖处理人脐静脉内皮细胞(HUVECs)和小鼠原代主动脉内皮细胞，建立糖尿病相关内皮功能障碍细胞模型，通过RT-qPCR、western blot和免疫荧光验证BASP1的表达变化。通过siRNA或过表达质粒沉默或过表达BASP1，检测其对细胞迁移、凋亡、小管形成、炎症反应和ROS的影响。发现了BASP1可能的信号通路，并利用EGFR抑制剂吉非替尼探讨了BASP1促进内皮功能障碍进展的机制。结果生物信息学分析表明，糖尿病合并冠心病患者中BASP1表达升高。高糖诱导内皮细胞中BASP1表达上调，且呈时间依赖关系。沉默BASP1可减轻高糖对内皮细胞的损伤。BASP1正调控EGFR。BASP1对内皮细胞凋亡的促进作用可能通过调控EGFR通路来实现。结论BASP1促进糖尿病患者高糖诱导的内皮细胞损伤，可能通过激活EGFR通路而被激活。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Diabetes Investigation Medicine-Internal Medicine

自引率

9.40%

发文量

218

期刊介绍： Journal of Diabetes Investigation is your core diabetes journal from Asia; the official journal of the Asian Association for the Study of Diabetes (AASD). The journal publishes original research, country reports, commentaries, reviews, mini-reviews, case reports, letters, as well as editorials and news. Embracing clinical and experimental research in diabetes and related areas, the Journal of Diabetes Investigation includes aspects of prevention, treatment, as well as molecular aspects and pathophysiology. Translational research focused on the exchange of ideas between clinicians and researchers is also welcome. Journal of Diabetes Investigation is indexed by Science Citation Index Expanded (SCIE).