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Research article2005Peer reviewedOpen access

A key role for mast cell chymase in the activation of pro-matrix metalloprotease-9 and pro-matrix metalloprotease-2

Tchougounova, Elena; Lundequist, Anders; Fajardo, Ignacio; Winberg, Jan-Olof; Åbrink, Magnus; Pejler, Gunnar

Abstract

Chymases, serine proteases exclusively expressed by mast cells, have been implicated in various pathological conditions. However, the basis for these activities is not known, i.e. the in vivo substrate(s) for mast cell chymase has not been identified. In this study we show that mice lacking the chymase mouse mast cell protease 4 (mMCP- 4) fail to process pro-matrix metalloprotease 9 (pro-MMP- 9) to its active form in vivo, whereas both the pro and active form of MMP-9 was found in tissues of wild type mice. Moreover, the processing of pro-MMP-2 into active enzyme was markedly defective in mMCP- 4 null animals. Histological analysis revealed an increase in collagen in the ear tissue of mMCP-4-deficient animals accompanied by increased ear thickness and a higher content of hydroxyproline. Furthermore, both lung and ear tissue from the knock-out animals showed a markedly increased staining for fibronectin. MMP-9 and MMP-2 are known to have a range of important activities, but the mechanisms for their activation in vivo have not been clarified previously. The present study thus indicates a key role for mast cell chymase in the regulation of pro-MMP-2 and -9 activities. Moreover, the results suggest an important role for mast cell chymase in regulating connective tissue homeostasis.

Published in

Journal of Biological Chemistry
2005, Volume: 280, number: 10, pages: 9291-9296
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

      SLU Authors

    • Tchougounova, Elena

      • Department of Molecular Biosciences, Swedish University of Agricultural Sciences

      • Lundequist, Anders

        • Department of Molecular Biosciences, Swedish University of Agricultural Sciences

        • Åbrink, Magnus

          • Department of Molecular Biosciences, Swedish University of Agricultural Sciences

          • Pejler, Gunnar

            • Department of Molecular Biosciences, Swedish University of Agricultural Sciences

          Associated SLU-program

          Future Animal Health and Welfare (until Jan 2017)

          UKÄ Subject classification

          Biochemistry and Molecular Biology

          Publication identifier

          DOI: https://doi.org/10.1074/jbc.M410396200

          Permanent link to this page (URI)

          https://res.slu.se/id/publ/41341