Abstract
Abstract
Background
Exosomes 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.
Methods
An 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.
Results
ADSCs-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.
Conclusion
ADSCs-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.
Funder
The Zhejiang Province Chinese Medicine Modernization Program
the Construction of Key Projects by Zhejiang Provincial Ministry
The Key Project of Scientific Research Foundation of Chinese Medicine
the “Pioneer” and “Leading Goose” R&D Program of Zhejiang
Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China
The Key project of Basic Scientific Research Operating Funds of Hangzhou Medical College
Publisher
Springer Science and Business Media LLC
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
2 articles.
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