| First Author | Folmsbee SS | Year | 2015 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 308 |
| Issue | 3 | Pages | L253-8 |
| PubMed ID | 25480337 | Mgi Jnum | J:227949 |
| Mgi Id | MGI:5704038 | Doi | 10.1152/ajplung.00331.2014 |
| Citation | Folmsbee SS, et al. (2015) The cardiac protein alphaT-catenin contributes to chemical-induced asthma. Am J Physiol Lung Cell Mol Physiol 308(3):L253-8 |
| abstractText | Ten to 25% of adult asthma is occupational induced, a subtype caused by exposure to workplace chemicals. A recent genomewide association study identified single-nucleotide polymorphisms in the cardiac protein alphaT-catenin (alphaT-cat) that correlated with the incidence and severity of toluene diisocyanate (TDI) occupational asthma. alphaT-cat is a critical mediator of cell-cell adhesion and is predominantly expressed in cardiomyocytes, but its connection to asthma remains unknown. Therefore, we sought to determine the primary alphaT-cat-expressing cell type in the lung and its contribution to lung physiology in a murine model of TDI asthma. We show that alphaT-cat is expressed in lung within the cardiac sheath of pulmonary veins. Mechanically ventilated alphaT-cat knockout (KO) mice exhibit a significantly increased pressure-volume curve area compared with wild-type (WT) mice, suggesting that alphaT-cat loss affects lung hysteresis. Using a murine model of TDI asthma, we find that alphaT-cat KO mice show increased airway hyperresponsiveness to methacholine compared with WT mice. Bronchoalveolar lavage reveals only a mild macrophage-dominant inflammation that is not significantly different between WT and KO mice. These data suggest that alphaT-cat may contribute to asthma through a mechanism independent of inflammation and related to heart and pulmonary vein dysfunction. |
