Inhibition of ADAM17 attenuates high glucose-induced angiogenesis and inflammation in endothelial cells partly through down-regulation of GRO-α/CXCR2 expression: implications in peritoneal dialysis.

IF 2.2 4区医学 Q2 UROLOGY & NEPHROLOGY

Clinical and Experimental Nephrology Pub Date : 2024-09-21 DOI:10.1007/s10157-024-02546-y

Na Jiang, Hao Feng, Weizhen Xie, Leyi Gu, Wei Fang, Tingting Ding, Jiangzi Yuan

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引用次数: 0

Abstract

Background: Angiogenesis and inflammation are key events leading to peritoneal morphologic alteration and ultrafiltration failure in patients undergoing peritoneal dialysis (PD). The current study aims to explore the role of ADAM17 in the angiogenetic and inflammatory responses of endothelial cells.

Methods: Human umbilical vein endothelial cells (HUVECs) were cultured and treated with a high glucose-containing medium. In parallel experiments, the expression of ADAM17 in HUVECs was inhibited by SiRNA interference. The mRNA and protein expression of ADAM17, GRO-α and CXCR2 were assessed by qPCR and Western blotting, respectively. The concentrations of GRO-α, VEGF, IL-6 and TNF-α in the cellular supernatants were determined by ELISA. Tube formation and migration of HUVECs were evaluated by Matrigel and transwell migration apparatus.

Results: High glucose increased the expression of ADAM17, CXCR2 and GRO-α in cultured HUVECs. RNA silencing of ADAM17 abolished high glucose-mediated increase of GRO-α and CXCR2, which were accompanied by reduced secretion of VEGF, IL-6, TNF-α, as well as tube formation and cell migration in HUVECs.

Conclusions: Inhibition of ADAM17 ameliorates high glucose-induced angiogenic and inflammatory responses in endothelial cells partly through down-regulation of GRO-α/CXCR2 expression.

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抑制 ADAM17 可部分通过下调 GRO-α/CXCR2 的表达减轻高血糖诱导的内皮细胞血管生成和炎症：对腹膜透析的影响。

背景：血管生成和炎症是导致腹膜透析（PD）患者腹膜形态改变和超滤失败的关键事件。本研究旨在探讨 ADAM17 在内皮细胞血管生成和炎症反应中的作用。在平行实验中，通过 SiRNA 干扰抑制 ADAM17 在 HUVECs 中的表达。分别通过 qPCR 和 Western 印迹法评估 ADAM17、GRO-α 和 CXCR2 的 mRNA 和蛋白表达。细胞上清液中 GRO-α、VEGF、IL-6 和 TNF-α 的浓度通过酶联免疫吸附测定。用 Matrigel 和 transwell 迁移仪评估 HUVECs 的管形成和迁移情况：结果：高糖增加了培养的 HUVECs 中 ADAM17、CXCR2 和 GRO-α 的表达。ADAM17的RNA沉默可抑制高糖介导的GRO-α和CXCR2的增加，同时降低血管内皮生长因子、IL-6、TNF-α的分泌，并减少HUVECs中管的形成和细胞迁移：结论：抑制ADAM17可部分通过下调GRO-α/CXCR2的表达改善高血糖诱导的内皮细胞血管生成和炎症反应。

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

Clinical and Experimental Nephrology UROLOGY & NEPHROLOGY-

CiteScore

4.10

自引率

4.30%

发文量

135

审稿时长

4-8 weeks

期刊介绍： Clinical and Experimental Nephrology is a peer-reviewed monthly journal, officially published by the Japanese Society of Nephrology (JSN) to provide an international forum for the discussion of research and issues relating to the study of nephrology. Out of respect for the founders of the JSN, the title of this journal uses the term “nephrology,” a word created and brought into use with the establishment of the JSN (Japanese Journal of Nephrology, Vol. 2, No. 1, 1960). The journal publishes articles on all aspects of nephrology, including basic, experimental, and clinical research, so as to share the latest research findings and ideas not only with members of the JSN, but with all researchers who wish to contribute to a better understanding of recent advances in nephrology. The journal is unique in that it introduces to an international readership original reports from Japan and also the clinical standards discussed and agreed by JSN.