| First Author | Prabhala P | Year | 2019 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 317 |
| Issue | 6 | Pages | L768-L777 |
| PubMed ID | 31553662 | Mgi Jnum | J:282011 |
| Mgi Id | MGI:6379184 | Doi | 10.1152/ajplung.00222.2019 |
| Citation | Prabhala P, et al. (2019) Laminin alpha4 contributes to airway remodeling and inflammation in asthma. Am J Physiol Lung Cell Mol Physiol 317(6):L768-L777 |
| abstractText | Airway inflammation and remodeling are characteristic features of asthma, with both contributing to airway hyperresponsiveness (AHR) and lung function limitation. Airway smooth muscle (ASM) accumulation and extracellular matrix deposition are characteristic features of airway remodeling, which may contribute to persistent AHR. Laminins containing the alpha2-chain contribute to characteristics of ASM remodeling in vitro and AHR in animal models of asthma. The role of other laminin chains, including the laminin alpha4 and alpha5 chains, which contribute to leukocyte migration in other diseases, is currently unknown. The aim of the current study was to investigate the role of these laminin chains in ASM function and in AHR, remodeling, and inflammation in asthma. Expression of both laminin alpha4 and alpha5 was observed in the human and mouse ASM bundle. In vitro, laminin alpha4 was found to promote a pro-proliferative, pro-contractile, and pro-fibrotic ASM cell phenotype. In line with this, treatment with laminin alpha4 and alpha5 function-blocking antibodies reduced allergen-induced increases in ASM mass in a mouse model of allergen-induced asthma. Moreover, eosinophilic inflammation was reduced by the laminin alpha4 function-blocking antibody as well. Using airway biopsies from healthy subjects and asthmatic patients, we found inverse correlations between ASM alpha4-chain expression and lung function and AHR, whereas eosinophil numbers correlated positively with expression of laminin alpha4 in the ASM bundle. This study, for the first time, indicates a prominent role for laminin alpha4 in ASM function and in inflammation, AHR, and remodeling in asthma, whereas the role of laminin alpha5 is more subtle. |
