| First Author | Courey AJ | Year | 2011 |
| Journal | Blood | Volume | 118 |
| Issue | 8 | Pages | 2313-21 |
| PubMed ID | 21734232 | Mgi Jnum | J:177097 |
| Mgi Id | MGI:5293599 | Doi | 10.1182/blood-2010-12-324574 |
| Citation | Courey AJ, et al. (2011) The vitronectin-binding function of PAI-1 exacerbates lung fibrosis in mice. Blood 118(8):2313-21 |
| abstractText | Plasminogen activator inhibitor-1 (PAI-1) is increased in the lungs of patients with pulmonary fibrosis, and animal studies have shown that experimental manipulations of PAI-1 levels directly influence the extent of scarring that follows lung injury. PAI-1 has 2 known properties that could potentiate fibrosis, namely an antiprotease activity that inhibits the generation of plasmin, and a vitronectin-binding function that interferes with cell adhesion to this extracellular matrix protein. To determine the relative importance of each PAI-1 function in lung fibrogenesis, we administered mutant PAI-1 proteins that possessed either intact antiprotease or vitronectin-binding activity to bleomycin-injured mice genetically deficient in PAI-1. We found that the vitronectin-binding capacity of PAI-1 was the primary determinant required for its ability to exacerbate lung scarring induced by intratracheal bleomycin administration. The critical role of the vitronectin-binding function of PAI-1 in fibrosis was confirmed in the bleomycin model using mice genetically modified to express the mutant PAI-1 proteins. We conclude that the vitronectin-binding function of PAI-1 is necessary and sufficient in its ability to exacerbate fibrotic processes in the lung. |
