| First Author | Zhang H | Year | 2023 |
| Journal | JCI Insight | Volume | 8 |
| Issue | 1 | PubMed ID | 36422999 |
| Mgi Jnum | J:339850 | Mgi Id | MGI:7433645 |
| Doi | 10.1172/jci.insight.151819 | Citation | Zhang H, et al. (2023) Gsk3beta regulates the resolution of liver ischemia/reperfusion injury via MerTK. JCI Insight 8(1) |
| abstractText | Although glycogen synthase kinase beta (Gsk3beta) 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 Gsk3beta inhibitory phosphorylation increased at both the early-activation and late-resolution stages of the disease. Myeloid Gsk3beta 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 Gsk3beta-KO mice in the activation of liver IRI. However, the resolution of liver IRI remained accelerated in Gsk3beta-KO mice. In CD11b-DTR mice, Gsk3beta-deficient BM-derived macrophages (BMMs) facilitated the resolution of liver IRI as compared with WT cells. Furthermore, Gsk3beta 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, Gsk3beta 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. |
