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PIM1–HDAC2 axis modulates intestinal homeostasis through epigenetic modification

Authors :
Jianming Yang
Yawen Xiao
Ningning Zhao
Geng Pei
Yan Sun
Xinyu Sun
Kaiyuan Yu
Chunhui Miao
Ran Liu
Junqiang Lv
Hongyu Chu
Lu Zhou
Bangmao Wang
Zhi Yao
Quan Wang
Source :
Acta Pharmaceutica Sinica B, Vol 14, Iss 7, Pp 3049-3067 (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

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.

Details

Language :
English
ISSN :
22113835
Volume :
14
Issue :
7
Database :
Directory of Open Access Journals
Journal :
Acta Pharmaceutica Sinica B
Publication Type :
Academic Journal
Accession number :
edsdoj.600ef25a0ab24748accbfae56660025e
Document Type :
article
Full Text :
https://doi.org/10.1016/j.apsb.2024.04.017