Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Nov 15, 2025; 16(11): 111223
Published online Nov 15, 2025. doi: 10.4239/wjd.v16.i11.111223
Published online Nov 15, 2025. doi: 10.4239/wjd.v16.i11.111223
RRM2 attenuates the renal tubular ferroptosis in diabetic kidney disease through PI3K/Akt/Nrf2 pathway
Chang-Chun Gao, Fen-Fen Ding, Xia Jiang, Department of Nephrology, Nantong Rehabilitation Hospital (Nantong Second People's Hospital), Nantong 226000, Jiangsu Province, China
Co-first authors: Chang-Chun Gao and Fen-Fen Ding.
Author contributions: Gao CC and Ding FF contribute equally to this study as co-first authors and they were involved in conceptualization, methodology, data curation, visualization, investigation, and writing-original draft; Jiang X was involved in project administration, supervision, funding acquisition, resources, writing-review & editing.
Institutional review board statement: This study was approved by the Nantong Second People's Hospital Ethics Committee (Approve No. 2025-024). The authors envisaged all standard protocols in accordance with the 1964 Declaration of Helsinki. In this study, all participants provided their written informed consent.
Conflict-of-interest statement: The authors declared no conflict of interest with other people or organizations.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author on 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: Xia Jiang, MD, Principal Investigator, Department of Nephrology, Nantong Rehabilitation Hospital (Nantong Second People's Hospital), No. 298 Xinhua Road, Chongchuan District, Nantong 226000, Jiangsu Province, China. orange1976@126.com
Received: June 26, 2025
Revised: August 18, 2025
Accepted: September 24, 2025
Published online: November 15, 2025
Processing time: 141 Days and 20.5 Hours
Revised: August 18, 2025
Accepted: September 24, 2025
Published online: November 15, 2025
Processing time: 141 Days and 20.5 Hours
Core Tip
Core Tip: Ribonucleotide reductase regulatory subunit M2 (RRM2) mitigates diabetic kidney disease (DKD) by inhibiting renal tubular ferroptosis via the PI3K/Akt/Nrf2 pathway. Elevated RRM2 levels in patients with type 2 diabetes mellitus are correlated with disease progression. Overexpression reduced oxidative stress, enhanced antioxidant markers [superoxide dismutase, glutathione (GSH), and GSH peroxidase 4], and suppressed ferroptosis (lower malondialdehyde and Fe2+ levels). RRM2 also activates PI3K/Akt signaling and promotes cell survival. Targeting RRM2 may offer therapeutic potential for preventing DKD progression.