Lung

, Volume 184, Issue 1, pp 15–19

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

  • Takashi Ishida
  • Hiroki Tsukada
  • Takashi Hasegawa
  • Hirohisa Yoshizawa
  • Fumitake Gejyo
Article

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 

References

  1. 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
  2. 2.
    Bienkowski RS, Gotkin MG (1995) Control of collagen deposition in mammalian lung. Proc Soc Exp Biol Med 209:118–140PubMedGoogle Scholar
  3. 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
  4. 4.
    Fukuda Y, IshizaM M, Kudoh S, Kitaichi M, Yamanaka N (1998) Localization of matrix metalloproteinases-1, -2, and -9 and tissue inhibitor of metalloproteinase-2 in interstitial lung diseases. Lab Invest 78:687–698PubMedGoogle Scholar
  5. 5.
    Fukuda Y, Mochimaru H, Terasaki Y, Kawamoto M, Kudoh S (2001) Mechanism of structural remodeling in pulmonary fibrosis. Chest 120(1 Suppl):41S–43SPubMedGoogle Scholar
  6. 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
  7. 7.
    Grant GA, Eisen AZ, Manner BL, Roswit WT, Goldberg GI (1987) The activation of human skin fibroblast procollagenase. Sequence identification of the major conversion products. J Biol Chem 262:5886–5889PubMedGoogle Scholar
  8. 8.
    Hasegawa T, Sorensen L, Dohi M, et al. (1997) Induction of urokinase-type plasminogen activator receptor by IL-1 beta. Am J Respir Cell Mol Biol 16:683–692PubMedGoogle Scholar
  9. 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
  10. 10.
    Koolwijk P, Miltenburg AM, van Erck MG, et al. (1995) Activated gelatinase-B (MMP-9) and urokinase-type plasminogen activator in synovial fluids of patients with arthritis. Correlation with clinical and experimental variables of inflammation. J Rheumatol 22:385–393PubMedGoogle Scholar
  11. 11.
    Kovacs EJ, DiPietro LA (1994) Fibrogenic cytokines and connective tissue production. FASEB J 8:854–61PubMedGoogle Scholar
  12. 12.
    Selman M, Pardo A (2002) Idiopathic pulmonary fibrosis: an epithelial fibroblastic cross-talk disorder. Respir Res 3:3CrossRefPubMedGoogle Scholar
  13. 13.
    Swaisgood CM, French EL, Noga C, Simon RH, Ploplis VA (2000) The development of bleomycin-induced pulmonary fibrosis in mice deficient for components of the fibrinolytic system. Am J Pathol 157:177–197PubMedGoogle Scholar
  14. 14.
    Tsukada H, Pourmotabbed T (2002) Unexpected crucial role of residue 272 in substrate specificity of fibroblast collagenase. J Biol, Chem 277:27378–27384CrossRefGoogle Scholar
  15. 15.
    Wilhelm SM, Collier IE, Kronberger A, et al. (1987) Human skin fibroblast stromelysin: structure, glycosylation, substrate specificity, and differential expression in normal and tumorigenic cells. Proc Natl Acad Sci USA 84:6725–6729PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Takashi Ishida
    • 1
  • Hiroki Tsukada
    • 1
  • Takashi Hasegawa
    • 1
  • Hirohisa Yoshizawa
    • 1
  • Fumitake Gejyo
    • 1
  1. 1.Division of Respiratory MedicineNiigata University Graduate School of Medical and Dental SciencesNiigataJapan

Personalised recommendations