Gsk3β regulates the resolution of liver ischemia/reperfusion injury via MerTK

Hanwen Zhang, Ming Ni, Han Wang, Jing Zhang, Dan Jin, Ronald W. Busuttil, Jerzy W. Kupiec-Weglinski, Wei Li, Xuehao Wang, Yuan Zhai

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Although glycogen synthase kinase β (Gsk3β) has been shown to regulate tissue inflammation, whether and how it regulates inflammation resolution versus inflammation activation is unclear. In a murine liver, partial warm ischemia/reperfusion injury (IRI) model, we found that Gsk3β inhibitory phosphorylation increased at both the early-activation and late-resolution stages of the disease. Myeloid Gsk3β deficiency not only alleviated liver injuries, it also facilitated the restoration of liver homeostasis. Depletion of Kupffer cells prior to the onset of liver ischemia diminished the differences between the WT and Gsk3β-KO mice in the activation of liver IRI. However, the resolution of liver IRI remained accelerated in Gsk3β-KO mice. In CD11b-DTR mice, Gsk3β-deficient BM-derived macrophages (BMMs) facilitated the resolution of liver IRI as compared with WT cells. Furthermore, Gsk3β deficiency promoted the reparative phenotype differentiation in vivo in liver-infiltrating macrophages and in vitro in BMMs. Gsk3 pharmacological inhibition promoted the resolution of liver IRI in WT, but not myeloid MerTK-deficient, mice. Thus, Gsk3β regulates liver IRI at both activation and resolution stages of the disease. Gsk3 inactivation enhances the proresolving function of liver-infiltrating macrophages in an MerTK-dependent manner.

Original languageEnglish (US)
Article numbere151819
JournalJCI insight
Volume8
Issue number1
DOIs
StatePublished - Jan 10 2023

ASJC Scopus subject areas

  • General Medicine

Fingerprint

Dive into the research topics of 'Gsk3β regulates the resolution of liver ischemia/reperfusion injury via MerTK'. Together they form a unique fingerprint.

Cite this