1999 Fiscal Year Final Research Report Summary
Pathobiology of Ito cells (hepatic stellate cells) with special reference to their myofibroblastic transformation in diseased livers
| Project/Area Number |
10670162
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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 |
Human pathology
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| Research Institution | Kochi Medical School |
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Principal Investigator |
ENZAN Hideaki Department of Pathology, Kochi Medical School Professor, 医学部, 教授 (00034645)
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| Project Period (FY) |
1998 – 1999
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| Keywords | liver fibrosis / Ito cell / hepatic stellate cell / myofibroblast / cellular transformation / TGF-β / α-smooth muscle actin / immunohistochemistry |
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| Research Abstract |
We previously demonstrated that α-smooth muscle actin (ASMA) is a useful phenotypic marker for both normal and transformed Ito cells in the adult human liver. In this study, we examined the mechanism of myofibroblastic transformation of Ito cells in human fibrotic livers and obtained the following results ;
1. In almost all types of liver fibrosis, such as hepatitic, posthepatitic, postnecrotic, alcoholic, cardiac and biliary fibrosis, the Ito cells in the areas of liver cell necrosis were always activated. They were swollen, proliferated actively and exhibited myofibroblastic transformation which were easily identified by the cytoplasmic overexpression of ASMA. These transformed Ito cells produced large amounts of collagen and other components of extracellular matrix, while the portal fibroblasts were not significantly associated with the development of liver fibrosis.
2. The myofibroblastic transformation of Ito cells was a basic, but strictly localized reaction following liver cell necrosis and appeared to be an initial and key event in liver fibrosis.
3. By innunohistochemistry and immunoelectron microscopy, we clear]y demonstrated the localization of transforming growth factor-β (TGF-β) and its latency-associated-peptide (LAP) and latent transforming growth factor binding protein (LTBP) in fibrotic human liver tissues, suggesting the close association of myofibroblastic transformation of Ito cells with the secretion of TGF-β and its activation.
Further studies are necessary to elucidate of the mechanism of TGF-βl activation in vivo and the analysis of its receptor's expression.
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[Publications] T. Saibara, K. Ookawauchi T. Yoshrkawa CL Ii, K, Tsuda, M. Ono, S. Iwasaki, T. Maeda, S. Onishi, E. Miyazaki, Y. Hayashi, M. Hiroi, H. Enzan: "Cationic amino acid transporter in rat Ito cells."Cells of the Hepatic Sinusoid. 7. 30-31 (1999)
Description
「研究成果報告書概要(欧文)」より
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