PKM2 deficiency promotes mucosal repair in ulcerative colitis by regu-lating macrophage polarization
10.3969/j.issn.1000-4718.2024.07.002
- VernacularTitle:PKM2缺失通过巨噬细胞极化促进溃疡性结肠炎黏膜修复
- Author:
Di ZHANG
1
;
Lijuan WANG
;
Chong LI
;
Haoxian CHEN
;
Hui YUAN
;
Jian HONG
;
Jinying LI
Author Information
1. 暨南大学基础医学院病理生理学系,广东 广州 510632
- Keywords:
ulcerative colitis;
macrophages;
pyruvate kinase M2;
mucosal repair
- From:
Chinese Journal of Pathophysiology
2024;40(7):1163-1172
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To clarify the effect of macrophage PKM2 deficiency on mucosal repair in ulcerative colitis(UC).METHODS:The gene expression and metabolic profiles in UC patients were first analyzed based on the following databases:PXD001608,GSE193677,and GSE214695.Using the macrophage-specific PKM2 elimination mice(PKM2ΔMAC),the functions of PKM2 in dextran sulfate sodium(DSS)-induced UC were clarified in vivo by analyzing the body weight,disease activity index(DAI)scores,HE staining,immunohistochemical staining,and expression of muco-sal barrier markers.The impact of PKM2 on macrophage polarization was also investigated by flow cytometry,RNA se-quencing and RT-qPCR in mouse bone marrow-derived macrophages(BMDMs)and THP-1 cells in vitro.RESULTS:Bioinformatic analysis suggested that the intestinal tissues of UC patients preferred glycolysis.The expression of PKM was parallel to the severity of UC in patients,and the expression of PKM2,but not PKM1,was elevated in macrophages of UC mice.In the DSS-induced UC mice,macrophage-specific PKM2 elimination significantly alleviates the body weight loss,diarrhea,rectal bleeding,colonic shorten,as well as decreased DAI scores and mucosal tissue damage.The BMDMs de-rived from the PKM2ΔMAC mice preferred the M2 polarization upon LPS or IL-4 stimulation to that derived from the wild-type mice,as indicated by the F4/80+CD45+CD86+and F4/80+CD45+CD206+population,as well as the expression of Ocln,F11r and Tjp-1.The RNA sequencing results indicated significant gene differential expression in PKM2 knockout mouse macrophages,which was enriched in biological processes such as leukocyte migration,tissue remodeling,and cytokine in-teractions.Macrophage PKM2 deficiency promoted the expression of mucosal repair factors(Il8,Cxcl1,Ptgs2 and Wnt6),which was further validated in PKM2 knockout THP-1 cells.CONCLUSION:The PKM2 deficiency in macro-phages benifits the mucosal repair in UC status via facilitating the wound-healing macrophage polarization.
