| First Author | Fan S | Year | 2022 |
| Journal | JCI Insight | Volume | 7 |
| Issue | 17 | PubMed ID | 35943805 |
| Mgi Jnum | J:344980 | Mgi Id | MGI:7345797 |
| Doi | 10.1172/jci.insight.158934 | Citation | Fan S, et al. (2022) Epithelial JAM-A is fundamental for intestinal wound repair in vivo. JCI Insight 7(17):e158934 |
| abstractText | Junctional adhesion molecule-A (JAM-A) is expressed in several cell types, including epithelial and endothelial cells, as well as some leukocytes. In intestinal epithelial cells (IEC), JAM-A localizes to cell junctions and plays a role in regulating barrier function. In vitro studies with model cell lines have shown that JAM-A contributes to IEC migration; however, in vivo studies investigating the role of JAM-A in cell migration-dependent processes such as mucosal wound repair have not been performed. In this study, we developed an inducible intestinal epithelial-specific JAM-A-knockdown mouse model (Jam-aERDeltaIEC). While acute induction of IEC-specific loss of JAM-A did not result in spontaneous colitis, such mice had significantly impaired mucosal healing after chemically induced colitis and after biopsy colonic wounding. In vitro primary cultures of JAM-A-deficient IEC demonstrated impaired migration in wound healing assays. Mechanistic studies revealed that JAM-A stabilizes formation of protein signaling complexes containing Rap1A/Talin/beta1 integrin at focal adhesions of migrating IECs. Loss of JAM-A in primary IEC led to decreased Rap1A activity and protein levels of Talin and beta1 integrin, and it led to a reduction in focal adhesion structures. These findings suggest that epithelial JAM-A plays a critical role in controlling mucosal repair in vivo through dynamic regulation of focal adhesions. |
