Podocyte SIRPα reduction in diabetic nephropathy aggravates podocyte injury by promoting pyruvate kinase M2 nuclear translocation

Podocyte SIRPα reduction in diabetic nephropathy aggravates podocyte injury by promoting pyruvate kinase M2 nuclear translocation

Podocyte injury is a critical event in the pathogenesis of diabetic nephropathy (DN). Hyperglycemia, oxidative stress, inflammation, and other factors contribute to podocyte damage in DN. In this study, we demonstrate that signaling regulatory protein alpha (SIRPα) plays a pivotal role in regulating...

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Bibliographic Details
Main Authors: Yang Chen, Mingchao Zhang, Ruoyu Jia, Bin Qian, Chenyang Jing, Caihong Zeng, Dihan Zhu, Zhihong Liu, Ke Zen, Limin Li
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Redox Biology
Subjects:
SIRPα
Podocyte injury
PKM2
Oxidative stress
Aerobic glycolysis
NF-κB
Online Access:http://www.sciencedirect.com/science/article/pii/S2213231724004178
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Summary:Podocyte injury is a critical event in the pathogenesis of diabetic nephropathy (DN). Hyperglycemia, oxidative stress, inflammation, and other factors contribute to podocyte damage in DN. In this study, we demonstrate that signaling regulatory protein alpha (SIRPα) plays a pivotal role in regulating the metabolic and immune homeostasis of podocytes. Deletion of SIRPα in podocytes exacerbates, while transgenic overexpression of SIRPα alleviates, podocyte injury in experimental DN mice. Mechanistically, SIRPα downregulation promotes pyruvate kinase M2 (PKM2) phosphorylation, initiating a positive feedback loop that involves PKM2 nuclear translocation, NF-κB activation, and oxidative stress, ultimately impairing aerobic glycolysis. Consistent with this mechanism, shikonin ameliorates podocyte injury by reducing PKM2 nuclear translocation, preventing oxidative stress and NF-κB activation, thereby restoring aerobic glycolysis.
ISSN:2213-2317

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