Matrix metalloproteinase-1 activation via plasmin generated on alveolar epithelial cell surfaces.
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.
Ishida
Takashi
T
Division of Respiratory Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, 951-8510, Niigata, Japan.
Tsukada
Hiroki
H
Hasegawa
Takashi
T
Yoshizawa
Hirohisa
H
Gejyo
Fumitake
F
D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D010958:Plasminogen / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000166:cytology
D024042:Collagen Type I; D005343:Fibrinolytic Agents; D010958:Plasminogen; D020781:Matrix Metalloproteinase 1