| First Author | Mitchell LA | Year | 2015 |
| Journal | Am J Pathol | Volume | 185 |
| Issue | 2 | Pages | 372-86 |
| PubMed ID | 25438062 | Mgi Jnum | J:218178 |
| Mgi Id | MGI:5616954 | Doi | 10.1016/j.ajpath.2014.10.010 |
| Citation | Mitchell LA, et al. (2015) Junctional adhesion molecule a promotes epithelial tight junction assembly to augment lung barrier function. Am J Pathol 185(2):372-86 |
| abstractText | Epithelial barrier function is maintained by tight junction proteins that control paracellular fluid flux. Among these proteins is junctional adhesion molecule A (JAM-A), an Ig fold transmembrane protein. To assess JAM-A function in the lung, we depleted JAM-A in primary alveolar epithelial cells using shRNA. In cultured cells, loss of JAM-A caused an approximately 30% decrease in transepithelial resistance, decreased expression of the tight junction scaffold protein zonula occludens 1, and disrupted junctional localization of the structural transmembrane protein claudin-18. Consistent with findings in other organs, loss of JAM-A decreased beta1 integrin expression and impaired filamentous actin formation. Using a model of mild systemic endoxotemia induced by i.p. injection of lipopolysaccharide, we report that JAM-A(-/-) mice showed increased susceptibility to pulmonary edema. On injury, the enhanced susceptibility of JAM-A(-/-) mice to edema correlated with increased, transient disruption of claudin-18, zonula occludens 1, and zonula occludens 2 localization to lung tight junctions in situ along with a delay in up-regulation of claudin-4. In contrast, wild-type mice showed no change in lung tight junction morphologic features in response to mild systemic endotoxemia. These findings support a key role of JAM-A in promoting tight junction homeostasis and lung barrier function by coordinating interactions among claudins, the tight junction scaffold, and the cytoskeleton. |
