| First Author | Morales-Nebreda LI | Year | 2015 |
| Journal | Am J Respir Cell Mol Biol | Volume | 52 |
| Issue | 4 | Pages | 503-12 |
| PubMed ID | 25188360 | Mgi Jnum | J:232283 |
| Mgi Id | MGI:5776440 | Doi | 10.1165/rcmb.2014-0057OC |
| Citation | Morales-Nebreda LI, et al. (2015) Lung-specific loss of alpha3 laminin worsens bleomycin-induced pulmonary fibrosis. Am J Respir Cell Mol Biol 52(4):503-12 |
| abstractText | Laminins are heterotrimeric proteins that are secreted by the alveolar epithelium into the basement membrane, and their expression is altered in extracellular matrices from patients with pulmonary fibrosis. In a small number of patients with pulmonary fibrosis, we found that the normal basement membrane distribution of the alpha3 laminin subunit was lost in fibrotic regions of the lung. To determine if these changes play a causal role in the development of fibrosis, we generated mice lacking the alpha3 laminin subunit specifically in the lung epithelium by crossing mice expressing Cre recombinase driven by the surfactant protein C promoter (SPC-Cre) with mice expressing floxed alleles encoding the alpha3 laminin gene (Lama3(fl/fl)). These mice exhibited no developmental abnormalities in the lungs up to 6 months of age, but, compared with control mice, had worsened mortality, increased inflammation, and increased fibrosis after the intratracheal administration of bleomycin. Similarly, the severity of fibrosis induced by an adenovirus encoding an active form of transforming growth factor-beta was worse in mice deficient in alpha3 laminin in the lung. Taken together, our results suggest that the loss of alpha3 laminin in the lung epithelium does not affect lung development, but plays a causal role in the development of fibrosis in response to bleomycin or adenovirally delivered transforming growth factor-beta. Thus, we speculate that the loss of the normal basement membrane organization of alpha3 laminin that we observe in fibrotic regions from the lungs of patients with pulmonary fibrosis contributes to their disease progression. |
