Altered Mucus Barrier Integrity and Increased Susceptibility to Colitis in Mice upon Loss of Telocyte Bone Morphogenetic Protein Signalling
| Autor: | Veronique Giroux, Nathalie Perreault, Vilcy Reyes Nicolás, Joannie M. Allaire, François Boudreau, Dianne Pupo Gómez, Alain B. Alfonso, Véronique Pomerleau |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
goblet cells
Colon QH301-705.5 Mice Transgenic Inflammation wound healing Bone morphogenetic protein inflammatory bowel diseases Article Pathogenesis 03 medical and health sciences 0302 clinical medicine Stress Physiological medicine Animals Telocytes O-glycosylation Colitis Biology (General) Myofibroblasts Bone Morphogenetic Protein Receptors Type I 030304 developmental biology 0303 health sciences Chemistry Mucins cellular microenvironment General Medicine medicine.disease Mucus Epithelium BMPR1A 3. Good health Cell biology Mice Inbred C57BL medicine.anatomical_structure 030220 oncology & carcinogenesis Bone Morphogenetic Proteins Disease Susceptibility medicine.symptom Wound healing Protein Processing Post-Translational Signal Transduction |
| Zdroj: | Cells, Vol 10, Iss 2954, p 2954 (2021) Cells Volume 10 Issue 11 |
| ISSN: | 2073-4409 |
| Popis: | FoxL1+-Telocytes (TCFoxL1+) are subepithelial cells that form a network underneath the epithelium. We have shown that without inflammatory stress, mice with loss of function in the BMP signalling pathway in TCFoxL1+ (BmpR1aΔFoxL1+) initiated colonic neoplasia. Although TCFoxL1+ are modulated in IBD patients, their specific role in this pathogenesis remains unclear. Thus, we investigated how the loss of BMP signalling in TCFoxL1+ influences the severity of inflammation and fosters epithelial recovery after inflammatory stress. BmpR1a was genetically ablated in mouse colonic TCFoxL1+. Experimental colitis was performed using a DSS challenge followed by recovery steps to assess wound healing. Physical barrier properties, including mucus composition and glycosylation, were assessed by alcian blue staining, immunofluorescences and RT-qPCR. We found that BmpR1aΔFoxL1+ mice had impaired mucus quality, and upon exposure to inflammatory challenges, they had increased susceptibility to experimental colitis and delayed healing. In addition, defective BMP signalling in TCFoxL1+ altered the functionality of goblet cells, thereby affecting mucosal structure and promoting bacterial invasion. Following inflammatory stress, TCFoxL1+ with impaired BMP signalling lose their homing signal for optimal distribution along the epithelium, which is critical in tissue regeneration after injury. Overall, our findings revealed key roles of BMP signalling in TCFoxL1+ in IBD pathogenesis. |
| Databáze: | OpenAIRE |
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