β-Arrestin-2 Enhances Endoplasmic Reticulum Stress-induced Glomerular Endothelial Cell Injury by Activating Transcription Factor 6 in Diabetic Nephropathy

Overview

Journal World J Diabetes

Publisher Baishideng Publishing Group

Specialty Endocrinology

Date 2024 Dec 16

PMID 39676815

Authors

Jiang Liu

Xiao-Yun Song

Xiu-Ting Li

Mu Yang

Fang Wang

Ying Han

Ying Jiang

Yu-Xin Lei

Miao Jiang

Wen Zhang

Dong-Qi Tang

Affiliations

Soon will be listed here.

Abstract

Background: Glomerular endothelial cell (GENC) injury is a characteristic of early-stage diabetic nephropathy (DN), and the investigation of potential therapeutic targets for preventing GENC injury is of clinical importance.

Aim: To investigate the role of β-arrestin-2 in GENCs under DN conditions.

Methods: Eight-week-old C57BL/6J mice were intraperitoneally injected with streptozotocin to induce DN. GENCs were transfected with plasmids containing siRNA-β-arrestin-2, shRNA-activating transcription factor 6 (ATF6), pCDNA-β-arrestin-2, or pCDNA-ATF6. Additionally, adeno-associated virus (AAV) containing shRNA-β-arrestin-2 was administered a tail vein injection in DN mice.

Results: The upregulation of β-arrestin-2 was observed in patients with DN as well as in GENCs from DN mice. Knockdown of β-arrestin-2 reduced apoptosis in high glucose-treated GENCs, which was reversed by the overexpression of ATF6. Moreover, overexpression of β-arrestin-2 Led to the activation of endoplasmic reticulum (ER) stress and the apoptosis of GENCs which could be mitigated by silencing of ATF6. Furthermore, knockdown of β-arrestin-2 by the administration of AAV-shRNA-β-arrestin-2 alleviated renal injury in DN mice.

Conclusion: Knockdown of β-arrestin-2 prevents GENC apoptosis by inhibiting ATF6-mediated ER stress and . Consequently, β-arrestin-2 may represent a promising therapeutic target for the clinical management of patients with DN.

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