MT-MMP, the cell surface activator of proMMP-2 (pro-gelatinase A), is expressed with its substrate in mouse tissue during embryogenesis

Hiroaki Kinoh, Hiroshi Sato, Yoshio Tsunezuka, Takahisa Takino, Atsuhiro Kawashima, Yasunori Okada, Motoharu Seiki

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143 Citations (Scopus)


Matrix metalloproteinases (MMPs), which degrade the components of the extracellular matrix, are key enzymes involved in the tissue remodeling of multicellular organisms. Since MMPs are secreted as inactive zymogens (pro-MMPs), they have to be activated to function. We identified a membrane-type MMP (MT-MMP) that activated proMMP-2 (pro-gelatinase A = 72 kDa type IV pro-collagenase) and described its expression on the invasive tumor cell surface. In this study we further examined the expression and role of MT-MMP in the activation of proMMP-2 during mouse embryogenesis. Northern blotting demonstrated that MT-MMP expression was increased together with that of MMP-2 and its inhibitor gene, TIMP-2, in embryos depending upon the number of days after gestation, and decreased with maturation after birth. In situ hybridization and immunohistochemistry localized MT-MMP mRNA and protein in the cells of ossifying tissues where both MMP-2 and TIMP-2 were expressed. Activated MMP-2 was detected by gelatin zymography in the lysates prepared from the micro dissected tissues that expressed the three genes. The activation rate of proMMP-2 was proportional to the expression of MMP-2 and MT-MMP. These results indicated that proMMP-2 activation through its activator, MT-MMP, is a physiological system used by organisms to initiate tissue remodeling on the cell surface.

Original languageEnglish
Pages (from-to)953-959
Number of pages7
JournalJournal of Cell Science
Issue number5
Publication statusPublished - 1996
Externally publishedYes


  • Embryogenesis
  • Gelatinase A
  • Membrane-type matrix metalloproteinase (MT-MMP)
  • Tissue remodeling

ASJC Scopus subject areas

  • Cell Biology


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