USP25-PKM2-glycolysis axis contributes to ischemia reperfusion-induced acute kidney injury by promoting M1-like macrophage polarization and proinflammatory response

M1-like macrophages have been reported to play critical roles in acute kidney injury (AKI). Here, we elucidated the role of ubiquitin-specific protease 25 (USP25) in M1-like macrophages polarization and AKI. High USP25 expression was correlated with a decline in renal function in patients with acute...

Full description

Saved in:
Bibliographic Details
Published in:Clinical immunology (Orlando, Fla.) Fla.), 2023-06, Vol.251, p.109279-109279, Article 109279
Main Authors: Yang, Yi, Zhan, Xiaona, Zhang, Cailin, Shi, Jia, Wu, Jianliang, Deng, Xuan, Hong, Yu, Li, Qing, Ge, Shuwang, Xu, Gang, He, Fan
Format: Article
Language:English
Subjects:
Acute Kidney Injury
Aerobic glycolysis
Animals
Glycolysis
Ischemia - metabolism
Ischemia-reperfusion
Kidney - metabolism
M1-like macrophage
Macrophages - metabolism
Mice
Mice, Inbred C57BL
Muscles
PKM2
Pyruvate Kinase - metabolism
Reperfusion
Reperfusion Injury - metabolism
Ubiquitin Thiolesterase - metabolism
Ubiquitin-specific protease 25
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:M1-like macrophages have been reported to play critical roles in acute kidney injury (AKI). Here, we elucidated the role of ubiquitin-specific protease 25 (USP25) in M1-like macrophages polarization and AKI. High USP25 expression was correlated with a decline in renal function in patients with acute kidney tubular injury and in mice with AKI. In contrast, USP25 knockout reduced M1-like macrophage infiltration, suppressed M1-like polarization, and improved AKI in mice, indicating that USP25 was necessary for M1-like polarization and proinflammatory response. Immunoprecipitation assay and liquid chromatography-tandem mass spectrometry showed that the M2 isoform of pyruvate kinase, muscle (PKM2) was a target substrate of USP25. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated the USP25 regulated aerobic glycolysis and lactate production during M1-like polarization via PKM2. Further analysis showed that the USP25-PKM2-aerobic glycolysis axis positively regulated M1-like polarization and exacerbated AKI in mice, providing potential therapeutic targets for AKI treatment.
ISSN:1521-6616
1521-7035
DOI:10.1016/j.clim.2023.109279