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World J Diabetes. Apr 15, 2026; 17(4): 115437
Published online Apr 15, 2026. doi: 10.4239/wjd.v17.i4.115437
Published online Apr 15, 2026. doi: 10.4239/wjd.v17.i4.115437
EP300 drives renal fibrosis in diabetic nephropathy via histone acetyltransferase-mediated nephrocystin-4 expression
Wei Si, Yao Dai, Qiu Zhang, Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
Wei Si, Guo-Ping Hu, Qiang Zhang, Fang Lv, Department of Endocrinology, Hefei First People’s Hospital, The Third Affiliated Hospital of Anhui Medical University, Hefei 230061, Anhui Province, China
Author contributions: Si W drafted the initial manuscript; Si W, Dai Y, Hu GP, Zhang Q, and Zhang Q collected clinical samples, conducted experiments, and acquired data; Si W, Hu GP, Lv F, and Zhang Q performed data processing, statistical analysis, and interpretation; Si W and Zhang Q designed the study and developed the overall research concept; Dai Y, Hu GP, Lv F, and Zhang Q critically reviewed the manuscript for important intellectual content; Zhang Q supervised the entire project and provided administrative and material support; all authors read and approved the final manuscript and agree to be accountable for all aspects of the work.
Supported by Anhui Province Traditional Chinese Medicine Inheritance and Innovation Research Project, No. 2024CCCX142.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Hefei First People’s Hospital. All procedures involving human participants were conducted in accordance with the Declaration of Helsinki and national guidelines for medical research involving human subjects.
Institutional animal care and use committee statement: All animal experiments were approved by the Institutional Animal Care and Use Committee of Hefei First People’s Hospital and were performed according to the National Institutes of Health guidelines for the care and use of laboratory animals.
Conflict-of-interest statement: The authors declare no conflict of interest in publishing the manuscript.
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 generated and analyzed during the current study contain clinical genetic information and are therefore not publicly available due to institutional privacy regulations and restrictions under the approved ethics protocol. Processed data supporting the findings of this study, including de-identified expression matrices and analytical code, are available from the corresponding author upon reasonable request.
Corresponding author: Qiu Zhang, MD, PhD, Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, No. 136 Jixi Road, Hefei 230022, Anhui Province, China. zhangqiu@ahmu.edu.cn
Received: October 16, 2025
Revised: December 3, 2025
Accepted: January 21, 2026
Published online: April 15, 2026
Processing time: 180 Days and 2.5 Hours
Revised: December 3, 2025
Accepted: January 21, 2026
Published online: April 15, 2026
Processing time: 180 Days and 2.5 Hours
Core Tip
Core Tip: Renal fibrosis is a key pathological process driving diabetic nephropathy progression, yet its epigenetic regulation remains unclear. This study identifies EP300 as a histone acetyltransferase that activates nephrocystin-4 transcription through Histone H3 lysine 27 acetylation, promoting renal fibrosis. Inhibition of the EP300-nephrocystin-4 axis alleviates fibrotic injury and improves renal function in diabetic mice, providing new mechanistic insight and a potential therapeutic target for diabetic nephropathy.