Perilipin 5 ameliorates high-glucose-induced podocyte injury via Akt/GSK-3β/Nrf2-mediated suppression of apoptosis, oxidative stress, and inflammation.

Abstract

Hyperglycemia-induced podocyte damage contributes to the onset of diabetic nephropathy, a severe complication of diabetes. Perilipin 5 (Plin5) exerts a vital role in numerous pathological conditions via affecting cell apoptosis, oxidative stress, and inflammation. However, whether Plin5 plays a role in regulating podocyte damage of diabetic nephropathy has not been fully determined. This work aimed to explore the role of Plin5 in mediating high glucose (HG)-induced injury of podocytes in vitro. Our results demonstrated that Plin5 expression was markedly decreased in mouse podocytes challenged with HG. Plin5 overexpression markedly suppressed HG-induced apoptosis, reactive oxygen species (ROS) production, and the pro-inflammatory response in podocytes. On the contrary, Plin5 silencing produced the opposite effects. Further mechanistic analysis demonstrated that Plin5 upregulation remarkably increased the levels of phospho-Akt and phospho-glycogen synthase kinase-3β (GSK-3β) in HG-exposed podocytes. Moreover, Plin5 overexpression increased the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and enhanced the activation of Nrf2 signaling. Akt inhibition markedly blocked Plin5-mediated activation of Nrf2, while GSK-3β inhibition reversed Plin5-silencing-induced suppressive effects on Nrf2 activation. Notably, Nrf2 suppression significantly blocked Plin5-mediated protective effects against HG-induced podocyte injury. In summary, our work indicates a vital role for Plin5 in protecting against HG-induced apoptosis, oxidative stress, and inflammation in podocytes via modulation of Akt/GSK-3β/Nrf2 signaling. This study suggests that Plin5 may participate in modulating podocyte damage in diabetic nephropathy.

• Authors: Jie Feng, Liyi Xie, Xiaoyang Yu, Chao Liu, Hongjuan Dong, Wanhong Lu, Ranran Kong
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 544 Pg. 22-30 (03 12 2021) ISSN: 1090-2104 [Electronic] United States
• PMID: 33516878 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Perilipin-5
• Reactive Oxygen Species
• Sweetening Agents
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, mouse
• Proto-Oncogene Proteins c-akt
• Glucose

Topics

• Animals
• Apoptosis
• Cells, Cultured
• Glucose (toxicity)
• Glycogen Synthase Kinase 3 beta (metabolism)
• Inflammation (drug therapy, metabolism, pathology)
• Kidney Diseases (metabolism, pathology, prevention & control)
• Mice
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress
• Perilipin-5 (pharmacology)
• Phosphorylation
• Podocytes (drug effects, metabolism, pathology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction
• Sweetening Agents (toxicity)