结肠炎
癌症研究
生物
SOCS3
促炎细胞因子
车站3
分子生物学
化学
免疫学
细胞生物学
炎症
信号转导
作者
Jiahong Li,Xiaohua Pan,Zhengnan Ren,Binbin Li,He Liu,Chengfei Wu,Xiaoliang Dong,Paul De Vos,Li‐Long Pan,Jia Sun
摘要
There is emerging evidence for a critical role for epigenetic modifiers in the development of inflammatory bowel disease (IBD). Protein arginine methyltransferase 2 (PRMT2) is responsible for the methylation of arginine residues on histones and targets transcription factors involved in many cellular processes, including gene transcription, mRNA splicing, cell proliferation, and cell differentiation. In this study, the role and underlying mechanisms of PRMT2 in colitis were studied.A mouse dextran sulfate sodium (DSS)-induced experimental colitis model was used to study PRMT2 in colitis. Lentivirus-induced PRMT2 silencing or overexpression in vivo was applied to address the role of PRMT2 in colitis. Detailed western blot and expression analysis were done to understand epigenetic changes induced by PRMT2 in colitis.PRMT2 is highly expressed in inflammatory bowel disease patients, in inflamed murine colon and in TNF-α stimulated murine gut epithelial cells. PRMT2 overexpression aggravates, while knockdown alleviates DSS-induced colitis, suggesting that PRMT2 is a pivotal mediator of colitis in mice. Mechanistically, PRMT2 mediates colitis by increasing repressive histone mark H3R8 asymmetric methylation (H3R8me2a) at the promoter region of the suppressor of cytokine signalling 3 promoter (SOCS3). Resultant inhibition of SOCS3 expression and inhibition of SOCS3-mediated degradation of TNF receptor associated factor 5 (TRAF5) via ubiquitination led to elevated TRAF5 expression and TRAF5-mediated downstream NF-κB/MAPK activation.Our study demonstrates that PRMT2 acts as a transcriptional co-activator for proinflammatory genes during colitis. Hence, targeting PRMT2 may provide a novel therapeutic approach for colitis.
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