Gene regulation by 3-D structure of extracellular matrix : a model for hepatic stellate cells

细胞外基质 3-D 结构的基因调控:肝星状细胞模型

基本信息

项目摘要

Interaction between cells and extracellular matrix (ECM) is essential for cell functions such as morphology, proliferation, motility, differentiation, and gene expression. The native form of type I collagen fibrils is known to affect these cell functions and ECM degrading enzymes such as matrix metalloprotease-2 (MMP-2, gelatinase A) and MMP-13 (collageanase-3) in several cell types. In this study we examined the roles of ECM components including type I collagen in the regulation of morphology and function of cultured hepatic stellate cells (HSCs). HSCs showed myofibroblast-like cell shapes with well-developed stress fibers when cultured on type I collagen coated surface, whereas rounded shapes when cultured on Matrigel, suggesting that HSCs recognize native structure of extracellular type I collagen fibrils and change their morphology and function. Then we examined the involvement of intracellular signaling including protein kinases, PI-3 kinase, small G-proteins, microtubule-associat … More ed protein (MAP2), and cytoskeleton reorganization in HSCs cultured on type I collagen gel. Several mRNA species including SP1, BCRP, dystonin, KIF1, and KAP3B were differentially regulated by extracellular type I collagen. These results indicated that cell surface-binding to extracellular interstitial collagen may trigger intracellular signaling and alteration in gene expression of cytoskeleton-related proteins, and finally induced cytoskeleton reorganization of process elongation. Gelatin zymography of the conditioned media revealed that pro and active forms of MMP-2 was increased in the HSCs cultured on type I collagen gel but not gelatin-, or type IV collagen-coated surface or Matrigel, suggesting the importance of the native form of type I collagen fibrils in pro-MMP-2 activation. RT-PCR analysis indicated that MMP-2, MT1-MMP and TIMP-2 mRNA levels were elevated in HSCs cultured on type I collagen gel. Therefore, the native fibrillar but not monomeric form of type I collagen induced pro-MMP-2 production and activation through MT1-MMP and TIMP-2 in cultured HSCs. Less
细胞与细胞外基质(ECM)之间的相互作用对于细胞功能如形态、增殖、运动、分化和基因表达是必不可少的。已知I型胶原原纤维的天然形式影响这些细胞功能和ECM降解酶,例如几种细胞类型中的基质金属蛋白酶-2(MMP-2,明胶酶A)和MMP-13(胶原酶-3)。在这项研究中,我们研究了ECM成分,包括I型胶原在培养的肝星状细胞(HSC)的形态和功能的调节作用。当在I型胶原包被的表面上培养时,HSC显示出具有发育良好的应力纤维的成肌纤维细胞样细胞形状,而当在Matrigel上培养时,HSC显示出圆形形状,这表明HSC识别细胞外I型胶原原纤维的天然结构并改变其形态和功能。然后,我们检测了细胞内信号传导的参与,包括蛋白激酶、PI-3激酶、小G蛋白、微管相关蛋白、微管蛋白和微管蛋白。 ...更多信息 艾德蛋白(MAP 2),和细胞骨架重组的HSC在I型胶原凝胶上培养。包括SP1、BCRP、肌张力障碍蛋白、KIF 1和KAP 3B在内的几种mRNA种类受到细胞外I型胶原的差异调节。这些结果表明,细胞表面与细胞外间质胶原的结合可能引发细胞内信号传导和细胞因子相关蛋白基因表达的改变,最终诱导细胞骨架重组的过程延长。条件培养基的明胶酶谱显示,MMP-2的前体和活性形式在I型胶原凝胶上培养的HSC中增加,但在明胶或IV型胶原涂覆的表面或Matrigel上不增加,这表明I型胶原原纤维的天然形式在MMP-2前体活化中的重要性。RT-PCR分析显示,在I型胶原凝胶上培养的HSC中MMP-2、MT 1-MMP和TIMP-2 mRNA表达水平升高。因此,在培养的HSC中,天然的纤维状而非单体形式的I型胶原通过MT 1-MMP和TIMP-2诱导pro-MMP-2的产生和活化。少

项目成果

期刊论文数量(36)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Retinal is the essential form of retinoid for storage and transport in the adult of the ascidian Halocynthia roretzi
Role of hepatic stellate cell/hepatocyte interaction and activation of hepatic stellate cells in the early phase of liver regeneration in the rat
  • DOI:
    10.1016/j.jhep.2004.02.005
  • 发表时间:
    2004-06-01
  • 期刊:
  • 影响因子:
    25.7
  • 作者:
    Mabuchi, A;Mullaney, I;Wheatley, AM
  • 通讯作者:
    Wheatley, AM
Uptake of denatured collagen into hepatic stellate cells : evidence for the involvement of urokinase plasminogen activator receptor-associated protein/Endo 180.
肝星状细胞吸收变性胶原蛋白:尿激酶纤溶酶原激活剂受体相关蛋白/Endo 180参与的证据。
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Mousavi;S.A.;Sato;M.;Sporstol;M.;Smedsrod;B.;Berg;T.;Kojima;N.;Senoo;H.
  • 通讯作者:
    H.
Three-dimentional structure of extracellular matrix regulates gene expression in cultured stellate cells to induce process elongation
细胞外基质的三维结构调节培养星状细胞中的基因表达以诱导过程伸长
  • DOI:
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Li YN;Sakamoto H;Kawate T;Cheng CX;Li YC;Shimada O;Atsumi S;Sato M et al.
  • 通讯作者:
    Sato M et al.
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IRIE Toshiaki其他文献

IRIE Toshiaki的其他文献

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{{ truncateString('IRIE Toshiaki', 18)}}的其他基金

DEMELOPMENT OF RAKIOLABELED SMALLER ANTI-TENASCIN-CANTIBODY FOR CLINICAL USE
RAKIO标记的较小抗腱蛋白抗体的开发用于临床用途
  • 批准号:
    17390342
  • 财政年份:
    2005
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)

相似海外基金

The cadherin Desmoglein-2 controls cell spreading and extracellular matrix gene expression.
钙粘蛋白 Desmoglein-2 控制细胞扩散和细胞外基质基因表达。
  • 批准号:
    10653447
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    2023
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    $ 2.18万
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Engineering extracellular matrix factories to study how the cellular microenvironment regulates gene expression
设计细胞外基质工厂来研究细胞微环境如何调节基因表达
  • 批准号:
    1804151
  • 财政年份:
    2016
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Studentship
Regulation of morphology and gene expression in cultured hepatic stellate cells by three-dimensional structure of extracellular matrix
细胞外基质三维结构对培养肝星状细胞形态和基因表达的调控
  • 批准号:
    11680689
  • 财政年份:
    1999
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Influence of soft laser irradiation on gene expression of EGF receptor and extracellular matrix in epithelial keratinocytes.
软激光照射对上皮角质形成细胞EGF受体和细胞外基质基因表达的影响
  • 批准号:
    10671710
  • 财政年份:
    1998
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular architecture and gene expression of glomerular extracellular matrix.
肾小球细胞外基质的分子结构和基因表达。
  • 批准号:
    04404039
  • 财政年份:
    1992
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (A)
Effects of extracellular matrix on changes of phenotype and gene expression in vascular smooth muscle cells
细胞外基质对血管平滑肌细胞表型及基因表达变化的影响
  • 批准号:
    04670371
  • 财政年份:
    1992
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
EXTRACELLULAR MATRIX GENE EXPRESSION IN CORNEA
角膜细胞外基质基因表达
  • 批准号:
    2161443
  • 财政年份:
    1987
  • 资助金额:
    $ 2.18万
  • 项目类别:
EXTRACELLULAR MATRIX GENE EXPRESSION IN CORNEA
角膜细胞外基质基因表达
  • 批准号:
    3264216
  • 财政年份:
    1987
  • 资助金额:
    $ 2.18万
  • 项目类别:
EXTRACELLULAR MATRIX GENE EXPRESSION IN CORNEA
角膜细胞外基质基因表达
  • 批准号:
    3264215
  • 财政年份:
    1987
  • 资助金额:
    $ 2.18万
  • 项目类别:
EXTRACELLULAR MATRIX GENE EXPRESSION IN CORNEA
角膜细胞外基质基因表达
  • 批准号:
    3264217
  • 财政年份:
    1987
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    $ 2.18万
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