Editorial
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Apr 15, 2025; 16(4): 101994
Published online Apr 15, 2025. doi: 10.4239/wjd.v16.i4.101994
Exploring a novel mechanism for targeting β-arrestin-2 in the management of diabetic nephropathy
Na Liu, Wei-Tao Yan, Kun Xiong
Na Liu, Wei-Tao Yan, Kun Xiong, Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha 410013, Hunan Province, China
Author contributions: Liu N wrote the original draft; Yan WT reviewed and edited the manuscript; Xiong K was the senior author and provided supervision and validation of the writing; All authors have read and agreed to the published version of the manuscript.
Supported by National Natural Science Foundation of China, No. 82303047, No. 82372507, No. 82172196 and No. 32401046; and Natural Science Foundation of Hunan Province, No. 2022JJ40801.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Kun Xiong, PhD, Professor, Department of Anatomy and Neurobiology, School of Basic Medical Science, Central South University, No. 172 Tongzipo Road, Changsha 410013, Hunan Province, China. xiongkun2001@163.com
Received: October 14, 2024
Revised: January 4, 2025
Accepted: February 10, 2025
Published online: April 15, 2025
Processing time: 139 Days and 21.3 Hours
Abstract

Diabetic nephropathy (DN) is a well-known microvascular complication in patients with diabetes mellitus, which is characterized by the accumulation of extracellular matrix in the glomerular and tubulointerstitial compartments, along with the hyalinization of intrarenal vasculature. DN has recently emerged as a leading cause of chronic and end-stage renal disease. While the pathobiology of other diabetic microvascular complications, such as retinopathy, is largely understood and has reasonable therapeutic options, the mechanisms and management strategies for DN remain incompletely elucidated. In this editorial, we comment on the article by Liu et al, focusing on the mechanisms underlying the detrimental impact of β-arrestin-2 on the kidneys in the context of DN. The authors suggest that inhibiting β-arrestin-2 could alleviate renal damage through suppressing apoptosis of glomerular endothelial cells (GENCs), highlighting β-arrestin-2 as a promising therapeutic target for DN. The study proposed that β-arrestin-2 triggers endoplasmic reticulum (ER) stress via the ATF6 signaling pathway, thereby promoting GENC apoptosis and exacerbating DN progression. Given the novel and crucial role of β-arrestin-2 in ER stress-related DN, it is imperative to further explore β-arrestin-2, its roles in ER stress and the potential therapeutic implications in DN.

Keywords: Diabetes mellitus; Diabetic nephropathy; β-arrestin-2; Endoplasmic reticulum stress; ATF6 signaling pathway

Core Tip: Diabetic nephropathy (DN), a complication of diabetes mellitus, poses significant challenges in the management. Liu et al observed that β-arrestin-2 deteriorates DN through inducing endoplasmic reticulum (ER) stress, and inhibiting β-arrestin-2 may protect glomerular endothelial cells and mitigate DN progression by curbing ER stress. This research underscores the significance of ER stress in DN and reveals an innovative molecular pathway involving β-arrestin-2 that may contribute to DN progression, offering potential targets for therapeutic interventions. Nevertheless, further clinical validation and investigation are necessary to confirm the clinical application of these findings.