| Item type |
文献 / Documents(1) |
| 公開日 |
2021-11-01 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
|
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|
関連識別子 |
https://doi.org/10.1016/j.ajpath.2021.10.002 |
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|
関連名称 |
10.1016/j.ajpath.2021.10.002 |
| 出版タイプ |
|
|
出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| タイトル |
|
|
タイトル |
A novel mouse model of non-alcoholic steatohepatitis suggests that liver fibrosis initiates around lipid-laden macrophages |
| タイトル別表記 |
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その他のタイトル |
Liver fibrosis begins around macrophages |
| 著者 |
(市村)清水, 真祐子
ツチヤマ, ヨウスケ
モリモト, ユウキ
松本, 穣
小林, 智子
スミダ, サトシ
柿本, 拓海
尾矢, 剛志
小川, 博久
山下, 理子
マツダ, サトル
オオマガリ, カツヒサ
タイラ, シュウ
常山, 幸一
|
| 抄録 |
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内容記述 |
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. |
| 書誌情報 |
en : The American Journal of Pathology
巻 192,
号 1,
p. 31-42,
発行日 2021-10-25
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
00029440 |
| 収録物ID |
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収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA00520990 |
| 収録物ID |
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|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA12024839 |
| 出版者 |
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|
出版者 |
American Society for Investigative Pathology |
| 出版者 |
|
|
出版者 |
Elsevier |
| 権利情報 |
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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/ |
| EID |
|
|
識別子 |
382586 |
| 言語 |
|
|
言語 |
eng |
ajp_192_1_31.pdf (2.73 MB)
