Matrix Metalloproteinase-1 Activation via Plasmin Generated on Alveolar Epithelial Cell Surfaces
- 75 Downloads
Plasmin is a potent protease related to tissue repair/remodeling not by fibrinolysis alone but also by activation of cytokines such as transforming growth factor and hepatocyte growth factor and by activation of matrix metalloproteases. We examined whether matrix matalloproteinase-1 was activated via plasminogen activation on surfaces of cultured alveolar epithelial cells (A-549). Cells were cultured overnight with plasminogen, pro-matrix metalloproteinase-1, and type I collagen as a substrate. Sodium dodecil sulfate–polyacrylamide gel electrophoresis was used to detect type I collagen degradation in culture supernatant. Collagen degradation corresponded to cell surface plasmin generation. No such finding was seen in the absence of cells or plasminogen. Alveolar epithelial plasminogen activation is important in matrix metalloproteinase-1 activation and thus presumably in tissue remodeling in pulmonary fibrosing pulmonary diseases such as idiopathic pulmonary fibrosis.
KeywordsPlasminogen Plasmin Alveolar epithelial cells Matrix metalloproteinase Tissue remodeling
- 1.Baricos WH, Cortez SL, el-Dahr SS, Schnaper HW (1995) ECM degradation by cultured human mesangial cells is mediated by a PA/plasmin/MMP-2 cascade. Kidney Lit 47:1039–1047Google Scholar
- 3.Ellenrieder V, Hendler SF, Ruhland C, et al. (2001) TGF-beta-induced invasiveness of pancreatic cancer cells is mediated by matrix metalloproteinase-2 and the urokinase plasminogen activator system. Int J Cancer 93:204–211Google Scholar
- 6.Gaadek JE, Kelman JA, Fells G, et al. (1979) Collagenase in the lower respiratory tract of patients with idiopathic pulmonary fibrosis. N Engl J Med 301:737–742Google Scholar
- 9.He CS, Wilhelm SM, Pentland AP, et al. (1989) Tissue cooperation in a proteolytic cascade activating human interstitial collagenase. Proc Nati Acad Sci U S 86:2632–2636Google Scholar