Macrophage Populations, Myofibroblastic Cells, and Extracellular Matrix Accumulation in Chronically-Developing Rat Liver Cirrhosis Induced by Repeated Injection of Thioacetamide
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概要
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In order to clarify the cellular and molecular aspects in cirrhotic lesions, we investigated the response of macrophage populations, myofibroblastic cell development, and deposition of extracellular matrices (ECMs), as well as expression patterns of fibrogenic factors, in chronically-developing hepatic cirrhosis induced in rats by thioacetamide (TAA). As an animal model, male F344 rats were rendered cirrhotic by repeated intraperitoneal injection of TAA (100 mg/kg BW; twice a week), and were examined at post-first injection (PFI) weeks 1, 3, 5, 7, 10, 15, and 20. Histologically, hepatocyte degeneration became evident in the perivenular and periportal areas with time, and from PFI weeks 10 micronodular lesions separated by fibrous septa were developed. ECMs (collagen types I, III, and IV, fibronectin and laminin) deposited with advancing lesions. ED1-immunopositive exudate macrophages showed an increased number for 20 weeks. ED2-immunopositive Kupffer cells and antigen-presenting macrophages reacting to OX6 (MHC class II-recognized antibody) revealed a transiently increased number at PFI weeks 1 and 3; interestingly, Kupffer cells became hypertrophic with time. The number of myofibroblastic cells reacting to α-smooth muscle actin was increased from PFI week 1, with a peak at PFI week 10. The semiquantitative analysis by the reverse transcription polymerase chain reaction revealed that expressions of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) mRNAs could be increased for 20 weeks. These results indicated that different macrophage populations participated in chronically-developing rat hepatic cirrhosis with different kinetics patterns, and that these macrophages might be related to myofibroblastic cell development through the production of fibrogenic factors such as TGF-β1 and TNF-α.
- 日本毒性病理学会の論文
- 2002-03-25
著者
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Kotani Takao
大阪府立大学 獣医病理学
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Kotani Takao
Vet. Pathol. Osaka Pref. Uni.
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YAMATE JYOJI
Department of Veterinary Pathology, Graduate School of Agricultural Lifesciences
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KUWAMURA Mitsuru
Department of Veterinary Pathology, Graduate School of Agriculture and Biological Sciences, Osaka Pr
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KOTANI Takao
Department of Veterinary Pathology, Graduate School of Agriculture and Biological Sciences, Osaka Pr
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IDE Mika
Department of Veterinary Pathology, Graduate School of Agriculture and Biological Sciences, Osaka Pr
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MACHIDA Yuko
Department of Veterinary Pathology, Graduate School of Agriculture and Biological Sciences, Osaka Pr
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SAWAMOTO Osamu
Department of Veterinary Pathology, Graduate School of Agriculture and Biological Sciences, Osaka Pr
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NAKANISHI Masako
Department of Veterinary Pathology, Graduate School of Agriculture and Biological Sciences, Osaka Pr
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SAKUMA Sadashige
Department of Veterinary Pathology, Graduate School of Agriculture and Biological Sciences, Osaka Pr
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Nakanishi Masako
Department Of Veterinary Pathology Graduate School Of Agriculture And Biological Sciences Osaka Pref
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Kuwamura Mitsuru
Dept. Vet. Pathol. U. Of Osaka Pref.
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Sakuma Sadashige
Department Of Veterinary Pathology Graduate School Of Agriculture And Biological Sciences Osaka Pref
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Sakuma Sadashige
Dept. Vet. Pathol. U. Of Osaka Pref.
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Sakuma Sadashige
Department Of Veterinary Pathology College Of Agriculture Osaka Prefecture University
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Machida Yuko
Department Of Veterinary Pathology Graduate School Of Agriculture And Biological Sciences Osaka Pref
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Yamate J
大阪府立大学大学院生命環境科学研究科
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Yamate Jyoji
Department Of Veterinary Pathology Graduate School Of Agriculture And Biological Science Osaka Prefe
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Kuwamura Mitsuru
Vet. Pathol. Osaka Pref. Uni.
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Ide Mika
Safety Research Laboratory, Mitsubishi Tanabe Pharma Corporation
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YAMATE Jyoji
Department of Integrated Structural Biosciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University
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NAKANISHI Masako
Department of Integrated Structural Biosciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University
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KOTANI Takao
Vet. Pathol., Osaka Pref. Uni.
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KUWAMURA Mitsuru
Department of Integrated Structural Biosciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University
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Machida Yuko
Department of Ophthalmology, Hirosaki Universtiy School of Medicine
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Kotani Takao
Department of Applied Mathematics and Physics, Tottori University, Tottori 680-8552, Japan
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