Adipose-derived stem cell exosomes regulate Nrf2/Keap1 in diabetic nephropathy by targeting FAM129B

Diabetology & Metabolic Syndrome

Research

Juan Jin¹  Lanjun Fu¹  Wenfang He¹  Qiang He¹  Peiyao Ren²  Fengmei Qian²  Danna Zheng³ 

[1] Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine), 310000, Hangzhou, Zhejiang, China;The Second School of Clinical Medicine, Zhejiang Chinese Medical University, 310003, Hangzhou, Zhejiang, China;Urology & Nephrology Center, Department of Nephrology, Affiliated People’s Hospital, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, 310014, Hangzhou, Zhejiang, China;

关键词: Adipose-derived stem cells;    Exosomes;    Diabetic nephropathy;    Oxidative stress;    Inflammation;    Nrf2/Keap1 pathway;   

DOI  :  10.1186/s13098-023-01119-5

 received in 2023-01-12, accepted in 2023-06-19,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundExosomes from adipose-derived stem cells (ADSCs-Exos) have exhibited a therapeutic role in diabetic nephropathy (DN). Further studies are needed to investigate how ADSCs-Exos regulate oxidative stress and inflammation in high glucose-induced podocyte injury.MethodsAn enzyme-linked immunosorbent assay (ELISA) was used to detect cellular inflammation. Reactive oxygen species (ROS) levels were assessed using flow cytometry in podocytes with different treatments. A malondialdehyde (MDA) kit was used to evaluate the lipid peroxidation levels in podocytes and kidney tissues of mice. Western blotting and co-immunoprecipitation were performed to detect protein expression and protein-protein interactions.ResultsADSCs-Exos reversed oxidative stress and inflammation in podocytes and kidney tissues of DN mice induced by high glucose levels in vitro and in vivo. Interference with heme oxygenase-1 expression could reverse the improvement effect of ADSCs-Exos on oxidative stress induced by high glucose levels. Furthermore, high glucose inhibited nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression and promoted Kelch-like ECH-associated protein 1 (Keap1) protein expression in podocytes, as well as their binding ability. As a potential target for Nrf2/Keap1 pathway regulation, FAM129B expression in podocytes is regulated by high glucose and ADSCs-Exos. Moreover, FAM129B siRNA blocked the inhibitory effect of ADSCs-Exos on intracellular ROS and MDA upregulation induced by high glucose in podocytes.ConclusionADSCs-Exos regulate the Nrf2/Keap1 pathway to alleviate inflammation and oxidative stress in DN by targeting FAM129B, which may provide a potential therapeutic strategy for DN.

【 授权许可】

CC BY   
© The Author(s) 2023

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