Junctional Adhesion Molecule-A (JAM-A) reguliert die intestinale Barriere während Homöostase und Entzündung
Zusammenfassung der Projektergebnisse
Despite its ubiquitous expression and various roles in cells such as platelets and immune cells, little is known about the role of JAM-A on intestinal epithelial cells. While our previous work showed JAM-A regulates wound healing after scratch wounding by stabilizing levels of β1- integrin in transformed epithelial cells, the link between JAM-A and β1-integrin-dependent cell migration remain unknown. Of note, the role of JAM-A in intestinal wound repair and mechanisms regulating JAM-A mediated cell migration in vivo remain elusive. Here, we provide novel in vivo insights into how epithelial JAM-A promotes recovery from DSS-induced colitis, with a particular importance of epithelial JAM-A in mucosal healing after mechanical injury. Furthermore, we verfiy the effect of JAM-A on wound repair in primary intestinal epithelial cells. We demonstrate how JAM-A modulates levels of β1-integrin and focal adhesion formation in primary intestinal epithelial cells during cell migration and wound repair, suggesting that JAM-A facilitates cell migration by stabilizing β1-integrin levels. Furthermore, we show reduced expression levels of Talin in JAM-A deficient migrating primary intestinal epithelial cells after wounding, suggesting that JAM-A mediated cell migration may be mediated through Talin and β1-integrin. We demonstrate that Rap1, Talin and β1-integrin exist in a complex that can be pulled down by co-immunoprecipitation in primary intestinal epithelial cells, and we detected decreased levels of Rap1-pulled down Talin and β1-integrin in JAM-A deficient primary intestinal epithelial cells compared to controls. Together, these findings suggest that JAM-A may play an important role in epithelial cell migration during wound repair by directing Rap1-mediated recruitment of Talin and regulating stabilization and activation of β1-integrin in focal adhesions during cell migration and wound repair.
Projektbezogene Publikationen (Auswahl)
- Functional Assessment of Intestinal Permeability and Neutrophil Transepithelial Migration in Mice using a Standardized Intestinal Loop Model, J Vis Exp. 2021 Feb 11
Boerner et al.
(Siehe online unter https://doi.org/10.3791/62093) - Neutrophil expressed CD47 regulates CD11b/CD18-dependent neutrophil transepithelial migration in the intestine in vivo, Mucosal Immunol. 2021 Mar;14(2):331-341
Azcutia et al.
(Siehe online unter https://doi.org/10.1038/s41385-020-0316-4)
