Article

Lung

, Volume 184, Issue 1, pp 15-19

First online:

Matrix Metalloproteinase-1 Activation via Plasmin Generated on Alveolar Epithelial Cell Surfaces

  • Takashi IshidaAffiliated withDivision of Respiratory Medicine, Niigata University Graduate School of Medical and Dental Sciences
  • , Hiroki TsukadaAffiliated withDivision of Respiratory Medicine, Niigata University Graduate School of Medical and Dental Sciences Email author 
  • , Takashi HasegawaAffiliated withDivision of Respiratory Medicine, Niigata University Graduate School of Medical and Dental Sciences
  • , Hirohisa YoshizawaAffiliated withDivision of Respiratory Medicine, Niigata University Graduate School of Medical and Dental Sciences
  • , Fumitake GejyoAffiliated withDivision of Respiratory Medicine, Niigata University Graduate School of Medical and Dental Sciences

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Abstract

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.

Keywords

Plasminogen Plasmin Alveolar epithelial cells Matrix metalloproteinase Tissue remodeling