Acta Pharmaceutica Sinica B (Jul 2024)
PIM1–HDAC2 axis modulates intestinal homeostasis through epigenetic modification
- 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
Affiliations
- Jianming Yang
- Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Sciences, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China
- Yawen Xiao
- Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Sciences, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China
- Ningning Zhao
- Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Sciences, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China
- Geng Pei
- Department of Pathology, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center of Cancer, Tianjin 30060, China
- Yan Sun
- Department of Pathology, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center of Cancer, Tianjin 30060, China
- Xinyu Sun
- Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Sciences, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China
- Kaiyuan Yu
- Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Sciences, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China
- Chunhui Miao
- Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Sciences, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China
- Ran Liu
- Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Sciences, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China
- Junqiang Lv
- Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Sciences, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China
- Hongyu Chu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300070, China
- Lu Zhou
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300070, China
- Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin 300070, China
- Zhi Yao
- Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Sciences, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China; Corresponding authors.
- Quan Wang
- Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Sciences, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin 300070, China; Corresponding authors.
- Journal volume & issue
-
Vol. 14,
no. 7
pp. 3049 – 3067
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.
