Research Paper Volume 15, Issue 19 pp 10291—10306
Dendrobium officinale polysaccharide decreases podocyte injury in diabetic nephropathy by regulating IRS-1/AKT signal and promoting mitophagy
- 1 Department of Geriatric, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Furong, Changsha 410005, P.R. China
- 2 Department of Rehabilitation, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Furong, Changsha 410005, P.R. China
Received: April 18, 2023 Accepted: September 8, 2023 Published: October 8, 2023
https://doi.org/10.18632/aging.205075How to Cite
Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Backgrounds: High glucose (HG) caused oxidative stress and mitochondrial dysfunction, resulting in insulin resistance in podocytes, a key mechanism of diabetic nephropathy. Dendrobium officinale polysaccharide (DOP) was able to improve insulin resistance and antioxidant capability.
Objective: The purpose of this study is to explore the mechanism by which DOP decreases the podocyte injury induced by HG.
Methods: MPC5 cells were treated with HG, DOP, and IRS-1/2 inhibitor NT157. Afterwards, glucose consumption, generations of ROS and MDA were measured using the detection kits. Mitophagy was monitored using both MtphagTracyker and LysoTracker. The mitochondrial membrane potential was evaluated by JC-1 staining. DOP was also used in a mouse model of diabetes, with the measurements of urine albumin, blood creatinine and blood urea nitrogen.
Results: Treatment with DOP suppressed the HG-induced reduction of glucose consumption, the phosphorylation of IRS-1 (phospho Y632), AKT (phospho Ser473 and Thr308) and Nephrin. In addition, HG-induced augment of ROS and MDA, formation of γ-H2A.X foci and translocation of AKT to nucleus were inhibited by DOP. DOP enhanced mitophagy, which was associated with decreased mitochondrial membrane potential and ROS production. DOP conferred protective effect on podocyte in the diabetic mouse by reducing the albumin/creatinine ratio and blood urea nitrogen, and restoring Nephrin expression in podocytes.
Conclusions: DOP alleviates HG-induced podocyte injuryby regulating IRS-1/AKT signal and promoting mitophagy.