Non-muscle myosin heavy chain 9 maintains intestinal homeostasis by preventing epithelium necroptosis and colitis adenoma formation
| Autor: | Xintong Li, Jing-Dong Han, Siqi Li, Yalong Wang, Ye-Guang Chen, Yuan Liu, Yehua Li, Shan Wang, Quanlong Jiang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adenoma Paneth Cells colitis Necroptosis necroptosis Biology Biochemistry Cell junction Article Receptors G-Protein-Coupled Myh9 03 medical and health sciences 0302 clinical medicine Myosin Genetics medicine Animals Homeostasis Intestinal Mucosa intestinal stem cells Mice Knockout Myosin Heavy Chains Stem Cells Homozygote LGR5 Cell migration Cell Biology Intestinal epithelium Epithelium Cell biology Anti-Bacterial Agents Gastrointestinal Microbiome Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Colonic Neoplasms Stem cell 030217 neurology & neurosurgery Gene Deletion Developmental Biology |
| Zdroj: | Stem Cell Reports |
| ISSN: | 2213-6711 |
| Popis: | Summary Non-muscle myosin IIA plays an important role in cell adhesion, cell migration, and tissue architecture. We previously showed that low activity of the heavy chain of non-muscle myosin II Myh9 is beneficial to LGR5+ intestinal stem cell maintenance. However, the function of Myh9 in adult mouse intestinal epithelium is largely unclear. In this study, we used the inducible Villin-creERT2 knockout approach to delete Myh9 in adult mouse intestinal epithelium and observed that homozygous deletion of Myh9 causes colitis-like morphologic changes in intestine, leads to a high sensitivity to dextran sulfate sodium and promotes colitis-related adenoma formation in the colon. Myh9 deletion disturbs cell junctions and impairs intestinal lumen barrier integrity, promoting the necroptosis of epithelial cells. Consistently, these changes can be partially rescued by Ripk3 knockout. Our results indicate that Myh9 is required for the maintenance of intestinal epithelium integrity and the prevention of cell necroptosis. Graphical abstract Highlights • Homozygous deletion of Myh9 causes colitis-like phenotypes in intestine • Myh9 deficiency leads to reduced Lgr5+ cell population and Paneth cell dislocation • Myh9 is critical for maintenance of intestinal epithelium integrity • Myh9 deletion results in high sensitivity to DSS and colitis adenomas formation Wang et al. report that Myh9 is required for maintenance of intestinal epithelial integrity mainly by preventing cell necroptosis and inflammation. Myh9 deficiency leads to cell junction disruption and colitis-like phenotypes and related adenomas development. |
| Databáze: | OpenAIRE |
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