title: MT-MMP, the cell surface activator of proMMP-2 (pro-gelatinase A), is expressed with its substrate in mouse tissue during embryogenesis.
abstract: 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.
authors: Departments of Molecular Virology & Oncology, Kanazawa University, Ishikawa, Japan.
authors: H
authors: H
authors: Kinoh
authors: H
authors: H
authors: Sato
authors: Y
authors: Y
authors: Tsunezuka
authors: T
authors: T
authors: Takino
authors: A
authors: A
authors: Kawashima
authors: Y
authors: Y
authors: Okada
authors: M
authors: M
authors: Seiki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005314:Embryonic and Fetal Development / Q000502:physiology; D004792:Enzyme Precursors / Q000378:metabolism*; D018093:Gelatinases / Q000032:analysis* / Q000037:antagonists & inhibitors; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020778:Matrix Metalloproteinase 2; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000494:pharmacology*; D011506:Proteins / Q000032:analysis*; D012333:RNA, Messenger / Q000096:biosynthesis; D013379:Substrate Specificity; D019716:Tissue Inhibitor of Metalloproteinase-2
chemical_list: D004792:Enzyme Precursors; D011480:Protease Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; C069860:progelatinase; D020778:Matrix Metalloproteinase 2