General Control Nonderepressible 2 Promotes M2 Macrophages Polarization and Renal Function After Sepsis-Induced Renal Injury

Abstract

The early metastasis of inflammatory M1 macrophages to M2 macrophages is an early marker for macrophages to play an anti-inflammatory role, while the role of macrophages in the kidney injury induced by sepsis is still poorly studied. We used septic serum to treat BMDMs at several time points, and then detect the expression of GCN2 in BMDMs. Western blot was used to detect the expression of iNos and Arg1 of macrophages. ELISA was used to detect the inflammatory cytokines. In vivo, the mice model of septic renal injury was established and immunohistochemistry was used to detect M1 and M2 markers, and IL-6 level. BUN, Scr and NAG were detected to assess renal function. The protein expression of GCN2 was increased in septic serum-stimulated BMDMs. WB results showed that GCN2 promote macrophage M1 to M2 polarization and decrease inflammation in vitro. GCN2 expression was increased in response to sepsis induced renal injury In vivo. When we overexpressed GCN2, there were more M1 polarizing to M2 and less inflammation, and it will improve renal function. Our study confirmed that increasing GCN2 expression can drive the polarization of M1 macrophages to M2, alleviate the renal inflammation and improve renal function induced by LPS.