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ID 116411
Title Alternative
Liver fibrosis begins around macrophages
Author
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
Content Type
Journal Article
Description
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.
Journal Title
The American Journal of Pathology
ISSN
00029440
NCID
AA00520990
AA12024839
Publisher
American Society for Investigative Pathology|Elsevier
Volume
192
Issue
1
Start Page
31
End Page
42
Published Date
2021-10-25
Remark
論文本文は2022-10-25以降公開予定
Rights
© 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/
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
language
eng
TextVersion
その他
departments
Medical Sciences
University Hospital