Roles of membrane-type matrix metalloproteinase in tissue organization.

膜型基质金属蛋白酶在组织组织中的作用。

• 批准号: 07457057
• 负责人: SEIKI Motoharu
• 金额: $ 5.06万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457057/
• 关键词: Matrix metalloproteinas; Membrane-type matrix metalloproteinase; Gelatinase A; TIMP-2; Mouse embryo; Tissue remodeling; マトリックスメタロプロテイナーゼ; セラチナーゼA; マトリックスメタロプロテアーゼ; 組織構築; マウス発生過程; トロフォブラスト

Matrix metalloproteinases (MMPs) are pivotal enzymes for tissue remodeling of multicellular organisms by degrading the components of extracellular matrix. Since MMPs are secreted as inactive zymogens (pro-MMPs), they have to be activated in the tissue to function. However little is known about physiological activators in vivo where active tissue remodeling is taking place. We recently identified a membrane-type MMP (MT-MMP) as an activator of pro-MMP-2 (pro-gelatinase A=72-kDa type IV pro-collagenase) that is expressed in invasive tumors and is responsible for degradation of type IV collagen in the basement membrane. In this study we examined whether MT-MMP plays a role in activating pro-MMP-2 during mouse embryogenesis. MT-MMP expression was increased together with that of MMP-2 and its inhibitor TIMP-2 in embryos according to the days after gestation and decreased with maturation after birth.MT-MMP transcripts and the product were localized in the cells of the occificating tissues where both MMP-2 and TIMP-2 were detected. Activated MMP-2 was detected in the lysate prepared from the microdissected tissue where expression of the three genes were observed. Activated MMP-2 was propotional to the expression of MMP-2 and MT-MMP.Thus the results indicate that MMP-2 and its activator MT-MMP is a widely used system for organisms to initiate tissue remodeling on the cell surface.

基质金属蛋白酶（MMP）是通过降解细胞外基质成分来进行多细胞生物组织重塑的关键酶。由于 MMP 作为无活性酶原（MMP 前体）分泌，因此它们必须在组织中被激活才能发挥作用。然而，人们对体内发生主动组织重塑的生理激活剂知之甚少。我们最近发现了一种膜型 MMP (MT-MMP) 作为 pro-MMP-2（原明胶酶 A=72-kDa IV 型前胶原酶）的激活剂，它在侵袭性肿瘤中表达并负责类型的降解。基底膜中的 IV 胶原蛋白。在这项研究中，我们检查了 MT-MMP 是否在小鼠胚胎发生过程中激活 pro-MMP-2 中发挥作用。 MT-MMP在胚胎中的表达随妊娠后天数的增加而与MMP-2及其抑制剂TIMP-2的表达一起增加，并随着出生后的成熟而减少。MT-MMP转录本及其产物定位于局灶组织的细胞中其中 MMP-2 和 TIMP-2 均被检测到。在从观察到三个基因表达的显微解剖组织制备的裂解物中检测到活化的MMP-2。激活的MMP-2与MMP-2和MT-MMP的表达成正比。因此，结果表明MMP-2及其激活剂MT-MMP是生物体广泛使用的启动细胞表面组织重塑的系统。

项目成果

佐藤 他: "MT-MMPs in tumor metastasis" J. Biochemistry. 119. 209-215 (1996)

Sato 等人：“肿瘤转移中的 MT-MMP”J. Biochemistry 119. 209-215 (1996)

常塚他: "Expression of MMI-MMP in tumor cells enhanc as pulmonary metastasis in an experivental wetastasis assay" Cancer Research. 56. 5678-5683 (1996)

Tsunetsuka 等人：“肿瘤细胞中 MMI-MMP 的表达增强了实验性湿转移测定中的肺转移”，Cancer Research 56. 5678-5683 (1996)。

喜納 他: "MT-MMP, The cell surface activator of proMMP-2, is expressed with its substrate in mouse tissue during embryogenesis" J. Cell. Science. 109. 953-959 (1996)

Kino 等人：“MT-MMP，proMMP-2 的细胞表面激活剂，在胚胎发生过程中与其底物一起在小鼠组织中表达”J. Cell Science。 109. 953-959 (1996)

喜納他: "MT-MMP,The cell surface activator of proMMP-2,is expressed with its substrate in mouse tissue,during embryegonesis" J.Cell.Science. 109. 953-959 (1996)

Kino 等人：“MT-MMP，proMMP-2 的细胞表面激活剂，在胚胎发育过程中与其底物一起在小鼠组织中表达”J.Cell.Science. 109. 953-959 (1996)

佐藤他: "MT-MMPs in tumor metastasis" J.Biochemistry. 119. 209-215 (1996)

Sato 等人：“肿瘤转移中的 MT-MMP”J.Biochemistry 119. 209-215 (1996)