2005 Fiscal Year Final Research Report Summary
Gene regulation by 3-D structure of extracellular matrix : a model for hepatic stellate cells
| Project/Area Number |
16590133
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General anatomy (including Histology/Embryology)
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| Research Institution | Hokkaido National College of Technology (2005)
Akita University (2004) |
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Principal Investigator |
IRIE Toshiaki Hokkaido National College of Technology, Professor, 教授 (90231167)
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| Co-Investigator(Kenkyū-buntansha) |
SENO Haruki Akita University School of medicine, Professor, 医学部, 教授 (90171355)
YOSHIKAWA Kiwamu Akita University School of Medicine, Research Associate, 医学部, 助手 (90400481)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Cell / Extracellular matrix / Gene expression / Collagen / Signal transport |
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| Research Abstract |
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
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[Journal Article] Vitamin A storage in hepatic stellate cells in the regenerating rat liver-with special reference to zonal heterogeneity-2005
Author(s)
Higashi, N., Sato, M., Kojima, N., Irie, T., Kawamura, K., Mabuchi, A., Senoo, H.
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Journal Title
Anatomical Record Part A 286(2)
Pages: 899-907
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Uptake of denatured collagen into hepatic stellate cells : evidence for the involvement of urokinase plasminogen activator receptor-associated protein/Endo 180.2005
Author(s)
Mousavi, S.A., Sato, M., Sporstol, M., Smedsrod, B., Berg, T., Kojima, N., Senoo, H.
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Journal Title
Biochemical Journal 387(1)
Pages: 39-46
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Vitamin A storage in hepatic stellate cells in the regenerating rat liver : with special reference to zonal heterogeneity.2005
Author(s)
Higashi, N., Sato, M., Kojima, N., Irie, T., Kawamura, K., Mabuchi, A., Senoo, H.
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Journal Title
Anat.Rec.Part A 286(2)
Pages: 899-907
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Degradation of extracellular matrix by extrahepatic stellate cells in the intestine of the lamprey, Lampetra japonica.2005
Author(s)
Higashi, N., Wake, K., Sato, M., Kojima, N., Imai, K., Senoo, H.
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Journal Title
Anat.Rec.Part A 285(1)
Pages: 668-675
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Uptake of denatured collagen into hepatic stellate cells : evidence for the involvement of urokinase plasminogen activator receptor-associated protein/Endo 180.2005
Author(s)
Mousavi, S.A., Sato, M., Sporstol, M., Smedsrod, B., Berg, T., Kojima, N., Senoo, H.
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Journal Title
Biochem.J. 387(1)
Pages: 39-46
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cell-cell junctions between mammalian (human and rat) hepatic stellate cells.2004
Author(s)
Higashi, N., Kojima, N., Miura, M., Imai, K., Sato, M., Senoo, H.
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Journal Title
Cell and Tissue Research 317(1)
Pages: 35-43
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Role of hepatic stellate cell/hepatocyte interaction and activation of hepatic stellate cells in the early phase of liver regeneration in the rat.2004
Author(s)
Mabuchi, A., Mullaney, I., Sheard, P.W., Hessian, P.A., Mallard, B.L., Tawadrous, M.N., Zimmermann, A., Senoo, H., Wheatley, A.M
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Journal Title
Journal of Hepatology 40(6)
Pages: 910-916
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Cell-cell junctions between mammalian (human and rat) hepatic stellate cells.2004
Author(s)
Higashi, N., Kojima, N., Miura, M., Imai, K., Sato, M., Senoo, H.
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Journal Title
Cell Tissue Res. 317(1)
Pages: 35-43
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Role of hepatic stellate cell/hepatocyte interaction and activation of hepatic stellate cells in the early phase of liver regeneration in the rat2004
Author(s)
Mabuchi, A., Mullaney, I., Sheard, P.W., Hessian, P.A., Mallard, B.L., Tawadrous, M.N., Zimmermann, A., Senoo, H., Wheatley, A.M
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Journal Title
J.Hepatol. 40(6)
Pages: 910-916
Description
「研究成果報告書概要(欧文)」より
