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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Oct 15, 2025; 16(10): 109782
Published online Oct 15, 2025. doi: 10.4239/wjd.v16.i10.109782
Published online Oct 15, 2025. doi: 10.4239/wjd.v16.i10.109782
Nicotinamide mononucleotide protects against diabetic nephropathy via IL-6/Rab5-mediated crosstalk between proximal tubular epithelial cells and podocytes
Dong-Qing Zha, Ping Gao, Xiao-Yan Wu, Division of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan 430070, Hubei Province, China
Co-corresponding authors: Ping Gao and Xiao-Yan Wu.
Author contributions: Gao P and Wu XY contribute equally to this study as co-corresponding authors; Zha DQ performed experimental work, data collection, and statistical analyses, and drafted the manuscript; Gao P designed and supervised the study, interpreted data, and critically revised the manuscript; Wu XY contributed to study conception, provided technical guidance, analyzed the experimental results, and critically revised the manuscript; all authors read and approved of the final manuscript.
Supported by Hubei Provincial Natural Science Foundation, No. 2023AFB732; and Scientific Research Project of Hubei Provincial Health Commission, No. WJ2023M053.
Institutional animal care and use committee statement: This study was approved by the Experimental Animal Welfare Ethics Committee Zhongnan Hospital of Wuhan University, Wuhan, China (No. ZN2023015) and performed in accordance with the guidelines of the National Health and Medical Research Council of China.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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 datasets used and/or analysed 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: Xiao-Yan Wu, MD, Division of Nephrology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuhan 430070, Hubei Province, China.
Received: May 22, 2025
Revised: July 2, 2025
Accepted: August 25, 2025
Published online: October 15, 2025
Processing time: 145 Days and 21.5 Hours
Revised: July 2, 2025
Accepted: August 25, 2025
Published online: October 15, 2025
Processing time: 145 Days and 21.5 Hours
Core Tip
Core Tip: This study identified a novel mechanism in diabetic nephropathy (DN), in which high glucose-induced interleukin-6 (IL-6) secretion by proximal tubular epithelial cells activated Rab5 signaling in podocytes, followed by nephrin endocytosis and structural damage. Importantly, nicotinamide mononucleotide (NMN) effectively interrupted this pathogenic IL-6/Rab5-mediated intercellular crosstalk, thereby preserving podocyte integrity, reducing glomerular injury, and decreasing albuminuria. These findings highlight NMN as a potential therapeutic strategy for mitigation of DN by targeting IL-6/Rab5 signaling.