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
- 批准号:08044262
- 负责人:
- 金额:$ 7.1万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for international Scientific Research
- 财政年份:1996
- 资助国家:日本
- 起止时间:1996 至 1997
- 项目状态:已结题
- 来源:
- 关键词:
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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- 影响因子:0
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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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- 影响因子:0
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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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- 影响因子:0
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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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- 影响因子:0
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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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