Application of a new cell-adhesive and cell-migatory molecule, laminin-5B, to regenerative medicine

新型细胞粘附和细胞迁移分子层粘连蛋白-5B在再生医学中的应用

基本信息

  • 批准号:
    17300157
  • 负责人:
  • 金额:
    $ 8.96万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
  • 财政年份:
    2005
  • 资助国家:
    日本
  • 起止时间:
    2005 至 2006
  • 项目状态:
    已结题

项目摘要

Laminins are a family of ECM proteins that are localized mainly in basement membranes and regulate various cellular functions such as adhesion, motility, proliferation, apoptosis and differentiation. More than 15 laminin isoforms consisting of different combinations of the three chains have been identified thus far. Among them, laminin-5 (α3A/B, β3, γ2 ; laminin-332), strongly promotes cellular adhesion and migration. Recently we established efficient expression systems of human recombinant laminin-5A (αA, β3, γ2) and laminin-5B (α3B, β3, γ2). In this study, we investigated the possibility to use these laminins for regenerative medicine. We also attempted to establish a system to produce a novel laminin isoform, laminin-6B (α3B, β1, γ1). Main results are as follows. 1) Mesenchymal stem cell (MSC) is thought to be an important cell type in the regenerative medicine, because it can differentiate into osteoblasts, chondrocytes, neural cells, muscle cells and some others. We found that laminin-5A and laminin-5B efficiently stimulated the growth of human MSCs in culture, while suppressing their chondrogenic differentiation. This suggest the possible use of laminin-5A/B as a growth-stimulatory supplement for the efficient in vitro growth of human MSCs. 2) The presence of laminin-6B is predicted, but it has never been identified. We found that this laminin existed in the basement membranes of micro-blood vessels in various human tissues. We also established an efficient expression system of this novel laminin by introducing cDNAs for human laminin α3B, β1, γ1 chains into HEK293 cells. (α3A, β3, γ2). This laminin may play an important role in angiogenesis and maintenance of vascular structures and functions.
层粘连蛋白(Laminins)是一个主要定位于基底膜的ECM蛋白家族,并调节多种细胞功能,如粘附、运动、增殖、凋亡和分化。到目前为止,已经鉴定出超过15种层粘连蛋白同工型,由这三条链的不同组合组成。其中,laminin-5 (α3A/B、β3、γ2; laminin-332)能强烈促进细胞粘附和迁移。近年来,我们建立了重组人laminin-5A (αA, β3, γ2)和laminin-5B (α3B, β3, γ2)的高效表达体系。在这项研究中,我们探讨了将这些层粘连蛋白用于再生医学的可能性。我们还试图建立一个系统,以产生新的层粘连蛋白异构体,层粘连蛋白6b (α3B, β1, γ1)。主要结果如下:1)间充质干细胞(Mesenchymal stem cell, MSC)可以分化为成骨细胞、软骨细胞、神经细胞、肌肉细胞等,被认为是再生医学中重要的细胞类型。我们发现laminin-5A和laminin-5B在培养中有效地刺激了人间充质干细胞的生长,同时抑制了它们的软骨分化。这表明可能使用层粘胶蛋白5a /B作为一种生长刺激补充剂,有效地促进人间充质干细胞的体外生长。2)预测了laminin-6B的存在,但从未被鉴定。我们发现这种层粘连蛋白存在于人体各种组织的微血管基底膜中。我们还通过将人层粘连蛋白α3B、β1、γ1链的cdna导入HEK293细胞,建立了该新型层粘连蛋白的高效表达体系。(α3a, β3, γ2)。这种层粘连蛋白可能在血管生成和维持血管结构和功能中起重要作用。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The short arm of laminin g2 chain of laminin-5 (laminin-332) binds syndecan-1 and regulates cellular adhesion and migration by suppressing phosphorylation of integrin b4 chain.
laminin-5 (laminin-332) 的层粘连蛋白 g2 链的短臂结合 syndecan-1,并通过抑制整合素 b4 链的磷酸化来调节细胞粘附和迁移。
  • DOI:
  • 发表时间:
    2007
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Ogawa;T.;Tsubota;Y.;Hashimoto;J.;Miyazaki;K.
  • 通讯作者:
    K.
Uncoordinated production of Laminin-5 chains in airways epithelium of allergic asthmatics.
  • DOI:
    10.1186/1465-9921-6-110
  • 发表时间:
    2005-09-22
  • 期刊:
  • 影响因子:
    5.8
  • 作者:
    Amin K;Janson C;Sevéus L;Miyazaki K;Virtanen I;Venge P
  • 通讯作者:
    Venge P
Binding of active matrilysin to cell surface cholesterol sulfate is essential for its membrane-associated proteolytic action and induction of homotypic cell adhesion.
活性基质溶解素与细胞表面硫酸胆固醇的结合对于其膜相关蛋白水解作用和同型细胞粘附的诱导至关重要。
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Yamamoto ;K.;Higashi;S.;Kioi;M.;Tsunezumi;J.;Honke;K.;Miyazaki;K.
  • 通讯作者:
    K.
Regulation of cell adhesion and type VII collagen binding by beta3 chain short arm of laminin-5: effect of its proteolytic cleavage.
层粘连蛋白 5 的 β3 链短臂对细胞粘附和 VII 型胶原蛋白结合的调节:其蛋白水解裂解的作用。
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Nakashima;Y.;Kariya;Y.;Yasuda;C.;Miyazaki;K.
  • 通讯作者:
    K.
The b3 chain short arm of laminin-332 (laminin-5) induces matrix assembly and cell adhesion activity of laminin-511 (laminin-10).
laminin-332 (laminin-5) 的 b3 链短臂诱导 laminin-511 (laminin-10) 的基质组装和细胞粘附活性。
  • DOI:
  • 发表时间:
    2007
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Nakashima;Y.;Kariya;Y.;Miyazaki;K.
  • 通讯作者:
    K.
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MIYAZAKI Kaoru其他文献

MIYAZAKI Kaoru的其他文献

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{{ truncateString('MIYAZAKI Kaoru', 18)}}的其他基金

Interaction of cancer cells with basement membrane proteins
癌细胞与基底膜蛋白的相互作用
  • 批准号:
    17014077
  • 财政年份:
    2005
  • 资助金额:
    $ 8.96万
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas
Structure and Function of Laminin-5, a Cell Adhesion Protein of Basement Membrane
基底膜细胞粘附蛋白Laminin-5的结构与功能
  • 批准号:
    11490030
  • 财政年份:
    1999
  • 资助金额:
    $ 8.96万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Regulatory mechanism of matrix metalloproteinase activity.
基质金属蛋白酶活性的调节机制。
  • 批准号:
    04680169
  • 财政年份:
    1992
  • 资助金额:
    $ 8.96万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Structures and functions of growth inhibitors secreted from rat liver cell lines
大鼠肝细胞系分泌的生长抑制剂的结构和功能
  • 批准号:
    63580123
  • 财政年份:
    1988
  • 资助金额:
    $ 8.96万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Molecular Diversity and Physiological Roles of Growth Inhibitors
生长抑制剂的分子多样性和生理作用
  • 批准号:
    63304060
  • 财政年份:
    1988
  • 资助金额:
    $ 8.96万
  • 项目类别:
    Grant-in-Aid for Co-operative Research (A)
Properties and Physiological Roles of Cell Growth Inhibitors Present in Blood
血液中细胞生长抑制剂的特性和生理作用
  • 批准号:
    60480500
  • 财政年份:
    1985
  • 资助金额:
    $ 8.96万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)

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