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Cell and Tissue Research

, Volume 315, Issue 1, pp 27–37 | Cite as

Overexpression of TIMP-1 under the MMP-9 promoter interferes with wound healing in transgenic mice

  • Tuire Salonurmi
  • Mataleena Parikka
  • Sirpa Kontusaari
  • Emma Pirilä
  • Carine Munaut
  • Tuula Salo
  • Karl TryggvasonEmail author
Regular Article

Abstract

We have generated transgenic mice harboring the murine matrix metalloproteinase 9 (MMP-9) promoter cloned in front of human TIMP-1 cDNA. The transgenic mice were viable and fertile and exhibited normal growth and general development. During wound healing the mice were shown to express human TIMP-1 in keratinocytes that normally express MMP-9. However, the healing of skin wounds was significantly retarded with slow migration of keratinocytes over the wound in transgenic mice. In situ zymography carried out on wound tissues revealed total blockage of gelatinolytic activity (i.e., MMP-9 and MMP-2). The results confirm studies with MMP-9 knockout mice showing that MMP-9 is not essential for general development, but they also demonstrate an important role of keratinocyte MMP-9, as well that of other keratinocyte MMPs that are inhibited by TIMP-1, in wound healing. The transgenic mice generated in this study provide a model for the role of MMPs in MMP-9-producing cells in other challenging situations such as bone fracture recovery and cancer invasion.

Keywords

Gene expression regulation Keratinocytes Matrix metalloproteinases Tissue inhibitor of metalloproteinase-1 Transgenic mice 

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Tuire Salonurmi
    • 1
  • Mataleena Parikka
    • 2
  • Sirpa Kontusaari
    • 1
  • Emma Pirilä
    • 3
  • Carine Munaut
    • 4
  • Tuula Salo
    • 2
    • 3
  • Karl Tryggvason
    • 5
    Email author
  1. 1.Biocenter Oulu, Department of BiochemistryUniversity of OuluOuluFinland
  2. 2.Department of DentistryUniversity of OuluOuluFinland
  3. 3.Department of DentistryUniversity of HelsinkiHelsinkiFinland
  4. 4.Department of Biology, Laboratory of Tumor and Developmental BiologyUniversity of LiegeLiegeBelgium
  5. 5.Division of Matrix Biology, Department of Medical Biochemistry and BiophysicsKarolinska InstituteStockholmSweden

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