| First Author | Chen H | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 12564 | PubMed ID | 27535718 |
| Mgi Jnum | J:241458 | Mgi Id | MGI:5902662 |
| Doi | 10.1038/ncomms12564 | Citation | Chen H, et al. (2016) Mechanosensing by the alpha6-integrin confers an invasive fibroblast phenotype and mediates lung fibrosis. Nat Commun 7:12564 |
| abstractText | Matrix stiffening is a prominent feature of pulmonary fibrosis. In this study, we demonstrate that matrix stiffness regulates the ability of fibrotic lung myofibroblasts to invade the basement membrane (BM). We identify alpha6-integrin as a mechanosensing integrin subunit that mediates matrix stiffness-regulated myofibroblast invasion. Increasing alpha6-expression, specifically the B isoform (alpha6B), couples beta1-integrin to mediate MMP-2-dependent pericellular proteolysis of BM collagen IV, leading to myofibroblast invasion. Human idiopathic pulmonary fibrosis lung myofibroblasts express high levels of alpha6-integrin in vitro and in vivo. Genetic ablation of alpha6 in collagen-expressing mesenchymal cells or pharmacological blockade of matrix stiffness-regulated alpha6-expression protects mice against bleomycin injury-induced experimental lung fibrosis. These findings suggest that alpha6-integrin is a matrix stiffness-regulated mechanosensitive molecule which confers an invasive fibroblast phenotype and mediates experimental lung fibrosis. Targeting this mechanosensing alpha6(beta1)-integrin offers a novel anti-fibrotic strategy against lung fibrosis. |
