Analyzes on ECM metabolism in transgenic and knockout mice

转基因和基因敲除小鼠 ECM 代谢分析

基本信息

项目摘要

Among the matrix metalloproteinase (MMP) gene family members, MMP-2 (gelatinase A) is believed to be involved in cancer invasion and metastasis and joint destruction, and thus its function in vivo is important. Membrane-type MMPs (MT-MMPs) were recently cloned as acribators of proMMP-2 and the degradation mechanism of extracellular matrix by the MT-MMPs/MMP-2 system is one of the key projects in the field of MMP research. In the present studies, we have demonstrated that proMMP-2 activation is mediated by MT1-MMP in the human invasive breast carcinomas and human thyroid carcinomas. In the human osteoarthritic and rheumatoid arhtritic cartilages, MT1-MMP also playd a major role in the activation of proMMP-2, showing a positive correlation with cartilage destruction. We also revealed that MT1-MMP is an extracellular matrix-degrading proteinase capable of digesting interstitial collagens and aggrecan as well as an activator of proMMP-2. MT3-MMP had a similar acitivity against these substrates except for type I collagen. Transgenic mice expressing MT1-MMP specifically in the cartilages are being made and analyzes of their phenotypes are now under way. These mice will be back crossed with MMP-2 knockout mice which had been made by a Japanese group and their phenotypes will be examined.
在基质金属蛋白酶(MMP)基因家族成员中,MMP-2(明胶酶A)被认为参与癌症侵袭和转移以及关节破坏,因此其在体内的功能是重要的。膜型基质金属蛋白酶(Membrane-type MMPs,MT-MMPs)是近年来发现的一种MMP-2前体的活性物质,其对细胞外基质的降解机制是MMP研究领域的热点之一。在本研究中,我们已经证明,proMMP-2的激活是由MT 1-MMP介导的人浸润性乳腺癌和人甲状腺癌。在人骨关节炎和类风湿关节炎软骨中,MT 1-MMP也在proMMP-2的激活中起主要作用,显示与软骨破坏正相关。我们还发现,MT 1-MMP是一种细胞外基质降解蛋白酶,能够消化间质胶原和聚集蛋白聚糖以及proMMP-2的激活剂。MT3-MMP对除I型胶原外的其他底物的活性相似。正在制造在软骨中特异性表达MT 1-MMP的转基因小鼠,并且正在对其表型进行分析。这些小鼠将与日本研究小组制造的MMP-2敲除小鼠回交,并检查其表型。

项目成果

期刊论文数量(11)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Nomura H., Fujimoto N., Seiki M., Mai M and Okada Y.: "Enhanced production of matrix metalloproteinases and activation of matrix metalloproteinase 2 (gelatinase A) in human gastric carcinomas." Int.J.Cancer. 69. 9-16 (1996)
Nomura H.、Fujimoto N.、Seiki M.、Mai M 和 Okada Y.:“增强人胃癌中基质金属蛋白酶的产生和基质金属蛋白酶 2(明胶酶 A)的激活。”
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Yamashita K., Azumano I., Mai M.and Okada Y.: "Expression and tissue localization of matrix metalloproteinase 7 (matrylysin) in human gastric carcinomas." Int.J.Cancer. (in press). (1998)
Yamashita K.、Azumano I.、Mai M. 和 Okada Y.:“基质金属蛋白酶 7(matrylysin)在人胃癌中的表达和组织定位。”
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Imai K.: "Degradation of decorin by matrix metalloproteinases.Identification of the cleavage sites,kinetic analyses and transforming growth factor-b1 release." Biochem.J.322. 809-814, (1997)
Imai K.:“基质金属蛋白酶对核心蛋白聚糖的降解。切割位点的鉴定、动力学分析和转化生长因子-b1 的释放。”
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Imai K., Hiramatsu A., Fukushima D., Pierschbacher M.D.and Okada Y.: "Degradation of decorin by matrix metalloproteinases. Identification of the cleavage sites, kinetic analyzes and transforming growth factor-b1 release" Biochem.J.322. 809-814 (1997)
Imai K.、Hiramatsu A.、Fukushima D.、Pierschbacher M.D. 和 Okada Y.:“基质金属蛋白酶对核心蛋白聚糖的降解。切割位点的鉴定、动力学分析和转化生长因子-b1 释放”Biochem.J.322。
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Ohta S., Imai K., Yamashita K., Matsumoto T., Azumano and Okada Y: "Expression of matrix metalloproteinase 7 (matrilysin) in human osteoarthritic cartilage." Lab Invest.(in press). (1998)
Ohta S.、Imai K.、Yamashita K.、Matsumoto T.、Azumano 和 Okada Y:“基质金属蛋白酶 7(基质溶解素)在人骨关节炎软骨中的表达。”
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OKADA Yasunori其他文献

OKADA Yasunori的其他文献

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{{ truncateString('OKADA Yasunori', 18)}}的其他基金

Pathological study on metalloproteinases in tissue remodeling under pathological conditions
病理条件下金属蛋白酶参与组织重塑的病理学研究
  • 批准号:
    24249022
  • 财政年份:
    2012
  • 资助金额:
    $ 7.1万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Study of integral transformations in hyperfunctions and differential operators of infinite order
超函数积分变换和无限阶微分算子的研究
  • 批准号:
    22540173
  • 财政年份:
    2010
  • 资助金额:
    $ 7.1万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Functional analyses and regulation of the metabolism of tissue microenvironmental factors by metalloproteinases
金属蛋白酶对组织微环境因子代谢的功能分析和调节
  • 批准号:
    19109004
  • 财政年份:
    2007
  • 资助金额:
    $ 7.1万
  • 项目类别:
    Grant-in-Aid for Scientific Research (S)
Pathological studies on the tissue destruction by metalloproteinases
金属蛋白酶组织破坏的病理学研究
  • 批准号:
    16209015
  • 财政年份:
    2004
  • 资助金额:
    $ 7.1万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Study of global solutions to Fuchsian equations and local solutions to linear PDE
Fuchsian方程全局解和线性偏微分方程局部解的研究
  • 批准号:
    15540156
  • 财政年份:
    2003
  • 资助金额:
    $ 7.1万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Research concerning Privacy Protection Principles about Data Transfer from EU to the United States
欧盟至美国数据传输隐私保护原则研究
  • 批准号:
    14520022
  • 财政年份:
    2002
  • 资助金额:
    $ 7.1万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Regulation of MT1-MMP gene expression by HMGI-C
HMGI-C对MT1-MMP基因表达的调控
  • 批准号:
    11694311
  • 财政年份:
    1999
  • 资助金额:
    $ 7.1万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Molecular Pathology of Cartilage destruction in Rheumatoid Arthritis
类风湿关节炎软骨破坏的分子病理学
  • 批准号:
    10470051
  • 财政年份:
    1998
  • 资助金额:
    $ 7.1万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Studies on the destruction of articular cartilage by matrix metalloproteinases
基质金属蛋白酶破坏关节软骨的研究
  • 批准号:
    07457049
  • 财政年份:
    1995
  • 资助金额:
    $ 7.1万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)

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In vivo calcium imaging during appetitive learning in HIV Tat transgenic mice exposed to cannabis
暴露于大麻的 HIV Tat 转基因小鼠食欲学习过程中的体内钙成像
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胆固醇相关基因对正常和转基因小鼠脑传入神经阻滞的反应
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Elucidation of the pathophysiology of schizophrenia / autism spectrum disorder using EP400 gene transgenic mice
使用 EP400 基因转基因小鼠阐明精神分裂症/自闭症谱系障碍的病理生理学
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研究转基因小鼠重复性轻度创伤性脑损伤的急性认知结果
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    486121
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胆固醇相关基因对正常和转基因小鼠脑传入神经阻滞的反应
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开发转基因小鼠来可视化线粒体应激,以了解与年龄相关的疾病的发病机制
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辛泽尔-吉迪翁综合征新疗法的开发和在人类细胞模型和转基因小鼠中的临床前测试
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Psmb8 突变转基因小鼠 Nakajo-Nishimura 综合征模型分析
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胆固醇相关基因对正常和转基因小鼠脑传入神经阻滞的反应
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