Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Mar 15, 2025; 16(3): 97544
Published online Mar 15, 2025. doi: 10.4239/wjd.v16.i3.97544
Published online Mar 15, 2025. doi: 10.4239/wjd.v16.i3.97544
NR4A1 silencing alleviates high-glucose-stimulated HK-2 cells pyroptosis and fibrosis via hindering NLRP3 activation and PI3K/AKT pathway
Jin-Meng Li, Lu Yuan, Jing Li, Wen-Yue Lv, Department of Clinical Medicine, Jining Medical University, Jining 272013, Shandong Province, China
Zi-Hua Song, Yuan Li, Han-Wen Chen, Han Li, Lei Liu, Na Wang, Department of General Medicine, Affiliated Hospital of Jining Medical University, Jining 272029, Shandong Province, China
Co-corresponding authors: Lei Liu and Na Wang.
Author contributions: Liu L and Wang N contribute equally to this study as co-corresponding authors; Wang N and Liu L designed the research; Li JM, Song ZH, Chen HW, Li Y and Li H performed the research; Li JM, Li J, Yuan L and Lv WY analyzed the data and prepared the figures; Li JM and Wang N wrote the manuscript; Wang N and Liu L contributed to the review and revision of this manuscript; all authors have read and approved the final manuscript.
Supported by Research Fund for Academician Lin He New Medicine, No. JYHL2022FMS02.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Ethics Committee of Medical Science Research of the Affiliated Hospital of Jining Medical University (Approval No. 2023-10-B008).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The original data can be obtained by contacting the corresponding author upon reasonable request.
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: Na Wang, Doctor, Additional Professor, Department of General Medicine, Affiliated Hospital of Jining Medical University, No. 89 Guhuai Road, Jining 272029, Shandong Province, China. wangna19840906@163.com
Received: June 2, 2024
Revised: October 15, 2024
Accepted: December 16, 2024
Published online: March 15, 2025
Processing time: 233 Days and 4.4 Hours
Revised: October 15, 2024
Accepted: December 16, 2024
Published online: March 15, 2025
Processing time: 233 Days and 4.4 Hours
Core Tip
Core Tip: This study demonstrated that nuclear receptor subfamily 4 group A member 1 (NR4A1) was upregulated in a rat model of diabetic kidney disease (DKD) and high-glucose-stimulated HK-2 cells. By transfecting siRNA of NR4A1, this study revealed that NR4A1 silencing attenuated DKD kidney pyroptosis and fibrosis in vitro. Mechanistically, silencing NR4A1 suppressed the activation of NOD-like receptor protein 3 and phosphoinositide 3-kinase/protein kinase B signaling pathways, which inhibited pyroptosis and fibrosis in vitro. These findings may provide a novel treatment strategy for patients with DKD.