| Project/Area Number |
13670176
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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 Kochi Medical School, Faculty of Medicine, Professor, 医学部, 教授 (00034645)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | liver fibrosis / heptic stellate cell / needle-biopsied liver tissue / TGF-β1 / immunohistochemistry / in situ hybridization / myofibroblast / ヒト肝組織 / C型慢性肝炎 / LTBP / 生検肝組織 / LAP / Smad |
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| Research Abstract |
TGF-β1 has a major role in liver fibrosis, especially in hepatic stellate cell (HSC) activation to myofibroblasts (MF) and in their overproduction of extracellular matrix. I and my co-workers examined the expression of TGF-β1 protein and mRNA in archival formalin -fixed, paraffin -embedded needle -biopsied liver tissues. Tissue -samples obtained from patients with chronic liver disease showed a variable degree of fibrosis.
Immunohistochemical analysis of TGF-β1 revealed mild to moderate immunoreactivity in infiltrating mononuclear cells in fibrotic lesions. MFs, possibly originated from HSCs, were also positive for TGF-β1. In addition, the biliary epithelial cells and hepatocytes adjacent to the fibrotic tissue showed the positive reaction. In situ hybridization with an oligonucleotide probe revealed TGF-β1 mRNA expression in infiltrating mononuclear cells as well as myofibroblast -like mesenchymal cells. Hepatocytes adjacent to the fibrotic tissue and some biliary epithelial cells also showed positive TGF-β1 mRNA signals.
These results suggest that TGF-β1 expression in the liver fibrosis is predominantly a function of infiltrating mononuclear cells and intrinsic mesenchymal cells as well as hepatocytes adjacent to the fibrotic tissue and biliary epithelial cells. MFs may be stimulated by paracrine and autocrine loops of TGF-β1, associated with the progression of liver fibrosis.
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