ID | 116411 |
タイトル別表記 | Liver fibrosis begins around macrophages
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著者 |
Tsuchiyama, Yosuke
Tokushima University
Morimoto, Yuki
Tokushima University
Sumida, Satoshi
Tokushima University
Kakimoto, Takumi
Tokushima University
Matsuda, Satoru
Nara Women's University
Omagari, Katsuhisa
University of Nagasaki
Taira, Shu
Fukushima University
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資料タイプ |
学術雑誌論文
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抄録 | Various cells such as macrophages and hepatic stellate cells interact in the generation of fibrosis in nonalcoholic steatohepatitis (NASH), but the mechanism remains unclear. We employed a high fat/cholesterol/cholate (HFCC) diet to generate a model of NASH-related fibrosis and investigate the pathogenesis of fibrosis. Two mouse strains differing in susceptibility to obesity, the susceptible strain C57BL/6J (B6) and the relatively resistant strain A/J, developed hepatic histological features of NASH including fat deposition, intralobular inflammation, hepatocyte ballooning, and fibrosis after 9 weeks of HFCC diet feeding. The severity of hepatic inflammation and fibrosis was greater in A/J mice than in B6 mice. A/J mice fed the HFCC diet exhibited characteristic CD204-positive lipid-laden macrophage aggregation in hepatic parenchyma. Polarized light visualized the Maltese cross, namely cholesterol crystals within the aggregated macrophages. Moreover, fibrosis developed in a ring-shape from the periphery of the aggregated macrophages, i.e., the starting point of fibrosis could be visualized histologically. Furthermore, matrix assisted laser desorption/ionization mass spectrometry imaging analysis detected a molecule at m/z 772.462, which corresponds to the protonated ion of phosphatidylcholine (P-18:1 (11Z)/18:0) and phosphatidylethanolamine (18:0/20:2 (11Z, 14Z)), in aggregated macrophages in adjacent to the fibrotic lesions. In conclusion, the present HFCC diet-fed A/J model provides an ideal tool to study fibrogenesis and enables novel insights into the pathophysiology of NASH-related fibrosis.
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掲載誌名 |
The American Journal of Pathology
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ISSN | 00029440
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cat書誌ID | AA00520990
AA12024839
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出版者 | American Society for Investigative Pathology|Elsevier
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巻 | 192
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号 | 1
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開始ページ | 31
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終了ページ | 42
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発行日 | 2021-10-25
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権利情報 | © 2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
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EDB ID | |
出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
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著者版フラグ |
著者版
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部局 |
医学系
病院
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