表观遗传学
平衡
生物
计算生物学
细胞生物学
生物信息学
遗传学
基因
作者
Jianming Yang,Yutao Xiao,Ningning Zhao,Geng Pei,Geng Pei,Geng Pei,Geng Pei,Yan Sun,Yan Sun,Yingxian Sun,Yingxian Sun,Xinyu Sun,Kaiyuan Yu,Chunhui Miao,Ran Liu,Junqiang Lv,Hongyu Chu,Lu Zhou,Bangmao Wang,Yang Liu,Quan Wang
标识
DOI:10.1016/j.apsb.2024.04.017
摘要
The mucosal barrier is crucial for intestinal homeostasis, and goblet cells are essential for maintaining the mucosal barrier integrity. The proviral integration site for Moloney murine leukemia virus-1 (PIM1) kinase regulates multiple cellular functions, but its role in intestinal homeostasis during colitis is unknown. Here, we demonstrate that PIM1 is prominently elevated in the colonic epithelia of both ulcerative colitis patients and murine models, in the presence of intestinal microbiota. Epithelial PIM1 leads to decreased goblet cells, thus impairing resistance to colitis and colitis-associated colorectal cancer (CAC) in mice. Mechanistically, PIM1 modulates goblet cell differentiation through the Wnt and Notch signaling pathways. Interestingly, PIM1 interacts with histone deacetylase 2 (HDAC2) and downregulates its level via phosphorylation, thereby altering the epigenetic profiles of Wnt signaling pathway genes. Collectively, these findings investigate the unknown function of the PIM1–HDAC2 axis in goblet cell differentiation and ulcerative colitis/CAC pathogenesis, which points to the potential for PIM1-targeted therapies of ulcerative colitis and CAC.
科研通智能强力驱动
Strongly Powered by AbleSci AI