التفاصيل البيبلوغرافية
| العنوان: |
PIM1–HDAC2 axis modulates intestinal homeostasis through epigenetic modification. |
| المؤلفون: |
Yang, Jianming, Xiao, Yawen, Zhao, Ningning, Pei, Geng, Sun, Yan, Sun, Xinyu, Yu, Kaiyuan, Miao, Chunhui, Liu, Ran, Lv, Junqiang, Chu, Hongyu, Zhou, Lu, Wang, Bangmao, Yao, Zhi, Wang, Quan |
| المصدر: |
Acta Pharmaceutica Sinica B; Jul2024, Vol. 14 Issue 7, p3049-3067, 19p |
| مصطلحات موضوعية: |
HOMEOSTASIS, NOTCH signaling pathway, ULCERATIVE colitis, CELL physiology, WNT signal transduction |
| مستخلص: |
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. PIM1 is upregulated in colonic epithelia during colitis. PIM1 modulates intestinal homeostasis through Wnt and Notch signaling pathways, partially mediated by its binding, phosphorylating, and downregulating of HDAC2. [Display omitted] [ABSTRACT FROM AUTHOR] |
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