Methyl-CpG-binding domain protein 2 contributes to renal fibrosis through promoting polarized M1 macrophages

• DOI: 10.1038/s41419-022-04577-3
• Publication Date: 2022-02-08T10:03:43Z
• Authors: Kai Ai; Jian Pan; Pan Zhang; Huiling Li; Zhibiao He; Hongliang Zhang; Xiaozhou Li; Yijian Li; Lei Yi; Ye Kang; Yinhuai Wang; Xudong Xiang; Xiangping Chai; Dongshan Zhang
• Keywords: CpG site

Abstract Recent studies reported that Methyl-CpG–binding domain protein 2 (MBD2) promoted M2 macrophages accumulation to increase bleomycin-induced pulmonary fibrosis. However, the role and mechanism of action MBD2 in differentiation renal fibrosis remain largely unknown. In current study, not only resting M0 polarized macrophages, but also induced them M1 transition macrophages. ChIP analysis demonstrated physically interacted with promoter region CpG islands G0S2 genes, then activated their expression by inducing hypomethylation region. Interestingly, data is consistent MBD2. Furthermore, Co-culture murine embryonic NIH 3T3 fibroblasts indicated mediated M1-induction ECM production via promotion G0S2. addition, we found inhibition suppressed LPS p53 as well activation stat3 RAW264.7 vivo, LysM cre attenuated unilateral ureteral obstruction (UUO) ischemia/reperfusion (I/R)-induced downregulation G0S2, which was fibronectin (FN), collagen I IV, α-SMA, These collectively contributed UUO I/R-induced through upregulation could be a target for treatment chronic kidney disease.