| First Author | Jara P | Year | 2015 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 308 |
| Issue | 6 | Pages | L511-22 |
| PubMed ID | 25575513 | Mgi Jnum | J:232276 |
| Mgi Id | MGI:5776433 | Doi | 10.1152/ajplung.00043.2014 |
| Citation | Jara P, et al. (2015) Matrix metalloproteinase (MMP)-19-deficient fibroblasts display a profibrotic phenotype. Am J Physiol Lung Cell Mol Physiol 308(6):L511-22 |
| abstractText | Idiopathic pulmonary fibrosis (IPF) is a progressive and usually lethal interstitial lung disease of unknown etiology characterized by aberrant activation of epithelial cells that induce the migration, proliferation and activation of fibroblasts. The resulting distinctive fibroblastic/myofibroblastic foci are responsible for the excessive extracellular matrix (ECM) production and abnormal lung remodeling. We have recently found that matrix metalloproteinase 19 (MMP-19)-deficient (Mmp19-/-) mice develop an exaggerated bleomycin-induced lung fibrosis, but the mechanisms are unclear. In this study, we explored the effect of MMP-19 deficiency on fibroblast gene expression and cell behavior. Microarray analysis of Mmp19-/- lung fibroblasts revealed the dysregulation of several profibrotic pathways, including ECM formation, migration, proliferation, and autophagy. Functional studies confirmed these findings. Compared with wild-type mice, Mmp19-/- lung fibroblasts showed increased alpha1 (I) collagen gene and collagen protein production at baseline and after transforming growth factor-beta treatment and increased smooth muscle-alpha actin expression (P < 0.05). Likewise, Mmp19-deficient lung fibroblasts showed a significant increase in proliferation (P < 0.01) and in transmigration and locomotion over Boyden chambers coated with type I collagen or with Matrigel (P < 0.05). These findings suggest that, in lung fibroblasts, MMP-19 has strong regulatory effects on the synthesis of key ECM components, on fibroblast to myofibroblast differentiation, and in migration and proliferation. |
