Publication Name	World Journal of Diabetes
Manuscript ID	112500
Country	China

Category	Pharmacology & Pharmacy
Manuscript Type	Basic Study
Article Title	Formononetin inhibits p53 signaling pathway activation to delay cellular senescence and ameliorates diabetic kidney disease
Manuscript Source	Unsolicited Manuscript
All Author List	Yue Ji, Rui-Xin Liu, Pei-Yue He, Yi-Min Zhou, Ya-Chun Li, Jing Guo, Bo Nie, Yu-Ning Liu and Wei-Jing Liu
Funding Agency and Grant Number	Funding Agency Grant Number National Natural Science Foundation of China Youth Program 82405313 National Natural Science Foundation of China Youth Program 82204821 National Natural Science Foundation of China Youth Program 82205037 National Natural Science Foundation of China 82274293 Dongzhimen Hospital Grant DZMG-XZYY-23002 Dongzhimen Hospital Grant DZMG-ZJXY-23004 Dongzhimen Hospital Grant DZMG-QNZX-24005 the China Postdoctoral Science Foundation 2024M760287 National Major Science and Technology Project 2025ZD0549600
Corresponding Author	Wei-Jing Liu, Academic Fellow, Professor, Institute of Nephrology & Beijing Key Laboratory, Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine, No. 5, Haiyuncang, Dongcheng District, Beijing, Beijing 100010, China. liuweijing-1977@hotmail.com
Key Words	Formononetin; Diabetic kidney disease; p53 signaling pathway; Cellular senescence; Transcriptomics
Core Tip	Transcriptomic profiling identified the p53 signaling pathway as the key mechanism through which formononetin (FN) alleviates diabetic kidney disease (DKD). FN upregulates MDM2 expression, thereby inhibiting p53 transcriptional activity—as confirmed by dual-luciferase reporter assay—and downregulating p21, leading to reduced senescence markers (β-galactosidase and senescence-associated secretory phenotype factors) in both podocytes and DKD mice. Notably, MDM2 gene silencing abrogates the anti-senescent effects of FN, establishing MDM2 as essential to its action. Overall, FN improves renal function and pathology by targeting the p53/MDM2/p21 axis to attenuate cellular senescence.
Citation	Ji Y, Liu RX, He PY, Zhou YM, Li YC, Guo J, Nie B, Liu YN, Liu WJ. Formononetin inhibits p53 signaling pathway activation to delay cellular senescence and ameliorates diabetic kidney disease. World J Diabetes 2025; In press

Received	2025-07-30 14:01
Peer-Review Started	2025-07-31 08:03
First Decision by Editorial Office Director	2025-09-04 07:09
Return for Revision	2025-09-04 07:09
Revised	2025-10-16 14:37
Publication Fee Transferred	2025-10-20 04:56
Second Decision by Editor	2025-12-18 02:37
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2025-12-18 06:09
Articles in Press	2025-12-18 06:09
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1948-9358 (online)
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