2. Academic Validation
  3. SIRT1-PINK1-Parkin axis orchestrated mitophagy and renal repair by dapagliflozin in diabetic nephropathy

SIRT1-PINK1-Parkin axis orchestrated mitophagy and renal repair by dapagliflozin in diabetic nephropathy

  • Biochim Biophys Acta Mol Basis Dis. 2025 Oct 15;1872(2):168074. doi: 10.1016/j.bbadis.2025.168074.
Yonggang Ma 1,  Na Luo 2,  Chenguang Yue 1,  Qiannan Sun 3,  Yangyang Wang 1,  Hongyan Zhao 1,  Ruilong Song 1,  Hui Zou 1,  Jiaqiao Zhu 1,  Zongping Liu 4
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009, PR China.
  • 2 Department of Endocrinology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, 211166, PR China; Department of Endocrinology, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, 225001, PR China.
  • 3 Medical Research Center, Northern Jiangsu People's Hospital, Yangzhou 225001, China.
  • 4 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009, PR China. Electronic address: liuzongping@yzu.edu.cn.
PMID: 41106506 DOI: 10.1016/j.bbadis.2025.168074
Abstract

Background: Mitochondrial dysfunction caused by metabolic stress is a key part of diabetic nephropathy. Dapagliflozin exerts significant hypoglycemic and nephroprotective effects; however, the precise mechanisms underlying its renoprotective actions remain to be fully elucidated.

Objective: This study aimed to elucidate the molecular mechanisms through which dapagliflozin mitigates diabetic nephropathy (DN), with particular emphasis on its regulatory role in the Sirt1-Pink1-Parkin axis and the restoration of mitochondrial homeostasis via Mitophagy.

Methods: Rats were fed a high-fat/high-sugar diet and streptozotocin. They were then divided into groups of various treatments. In vitro, high glucose-induced NRK-52E cell injury was treated with dapagliflozin. Evaluations included renal histopathology, urinary biomarkers, Apoptosis, Reactive Oxygen Species, mitochondrial membrane potential, and SIRT1/Pink1/Parkin pathway activation.

Results: Dapagliflozin exerted significant protective effects against streptozotocin-induced diabetic nephropathy. Dapagliflozin treatment in vitro restored mitochondrial membrane potential and reduced ROS levels in high glucose-induced NRK-52E cells. High glucose exposure markedly upregulated the expression of mitochondria-associated apoptotic proteins in NRK-52E cells, which was reduced by dapagliflozin. This study revealed that SIRT1/Pink1/Parkin-mediated Mitophagy was suppressed in DN and high glucose-induced NRK-52E cells but was activated following dapagliflozin treatment.

Conclusion: Our findings demonstrate that dapagliflozin modulates SIRT1/Pink1/Parkin-mediated mitochondrial Autophagy and effectively restores mitochondrial homeostasis in diabetic nephropathy. Modulating mitochondrial Autophagy through this pathway may serve as a promising therapeutic strategy for diabetic nephropathy.

Keywords

Dapagliflozin; Diabetic nephropathy; Mitochondrial quality control; Mitophagy; Sirt1/Pink1/Parkin pathway.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z