Regulation of intestinal barrier by Junctional Adhesion Molecule-A (JAM-A) during homeostasis and inflammation
Final Report Abstract
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.
Publications
- 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.
(See online at 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.
(See online at https://doi.org/10.1038/s41385-020-0316-4)
