RegⅢγ promotes the proliferation, and inhibits inflammation response of macrophages by Akt, STAT3 and NF-κB pathways.

As an inflammatory regulator, intestinal regenerating islet-derived 3 gamma (RegⅢγ) contributes to alleviating liver injury in liver diseases and colitis. However, it is unclear whether hepatic RegⅢγ exerts a vital impact on liver regeneration (LR). In this study, the expression profile and localization of RegⅢγ in LR were demonstrated by microarray analysis, qRT-PCR and immunofluorescence staining. Then, RAW264.7 cells with RegⅢγ deficiency and overexpression were obtained by the CRISPR/Cas9 system and lentivirus infection, respectively. MTT, flow cytometry, EdU, transwell, neutral red phagocytosis, and NO assays were performed to detect the functions of RegⅢγ in RAW264.7 cell proliferation and inflammation. Finally, the regulatory mechanism of RegⅢγ was explored by co-immunoprecipitation and Western blot assays. According to our findings, RegⅢγ showed significant expression changes in Kupffer cells during LR, and RegⅢγ overexpression stimulated the viability, proliferation, phagocytosis and migration of RAW264.7 cells, whereas RegⅢγ deficiency reversed these effects. Similarly, RegⅢγ overexpression facilitated the expression of HO-1 and IL-10, while RegⅢγ deficiency promoted NO production and p-Akt, p-STAT3, p-p65 and TNF-α expression. In conclusion, RegⅢγ may facilitate LR by promoting the proliferation of macrophages and inhibiting their inflammatory response through Akt, STAT3 and NF-κB pathways in the priming stage of LR.