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PLoS One. 2013 Dec 11;8(12):e82163. doi: 10.1371/journal.pone.0082163. eCollection 2013.

Hepatic crown-like structure: a unique histological feature in non-alcoholic steatohepatitis in mice and humans.

Author information

1
Department of Organ Network and Metabolism, Tokyo Medical and Dental University, Tokyo, Japan.
2
Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan ; Medical Research Laboratories, Shionogi & Co. Ltd., Osaka, Japan.
3
Department of Organ Network and Metabolism, Tokyo Medical and Dental University, Tokyo, Japan ; Japan Science and Technology Agency, PRESTO, Tokyo, Japan.
4
Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
5
Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
6
Heart Life Hospital, Okinawa, Japan.
7
Department of Home Economics, Otsuma Women's University, Tokyo, Japan.
8
Department of Polymer Chemistry, Kyoto University Graduate School of Engineering, Kyoto, Japan.
9
Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Abstract

Although macrophages are thought to be crucial for the pathogenesis of chronic inflammatory diseases, how they are involved in disease progression from simple steatosis to non-alcoholic steatohepatitis (NASH) is poorly understood. Here we report the unique histological structure termed "hepatic crown-like structures (hCLS)" in the mouse model of human NASH; melanocortin-4 receptor deficient mice fed a Western diet. In hCLS, CD11c-positive macrophages aggregate to surround hepatocytes with large lipid droplets, which is similar to those described in obese adipose tissue. Histological analysis revealed that hCLS is closely associated with activated fibroblasts and collagen deposition. When treatment with clodronate liposomes effectively depletes macrophages scattered in the liver, with those in hCLS intact, hepatic expression of inflammatory and fibrogenic genes is unaffected, suggesting that hCLS is an important source of inflammation and fibrosis during the progression of NASH. Notably, the number of hCLS is positively correlated with the extent of liver fibrosis. We also observed increased number of hCLS in the liver of non-alcoholic fatty liver disease/NASH patients. Collectively, our data provide evidence that hCLS is involved in the development of hepatic inflammation and fibrosis, thereby suggesting its pathophysiologic role in disease progression from simple steatosis to NASH.

PMID:
24349208
PMCID:
PMC3859576
DOI:
10.1371/journal.pone.0082163
[Indexed for MEDLINE]
Free PMC Article
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