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Hepatic Crown-Like Structure: A Unique Histological Feature in Non-Alcoholic Steatohepatitis in Mice and Humans

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 crow...

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Autores principales: Itoh, Michiko, Kato, Hideaki, Suganami, Takayoshi, Konuma, Kuniha, Marumoto, Yoshio, Terai, Shuji, Sakugawa, Hiroshi, Kanai, Sayaka, Hamaguchi, Miho, Fukaishi, Takahiro, Aoe, Seiichiro, Akiyoshi, Kazunari, Komohara, Yoshihiro, Takeya, Motohiro, Sakaida, Isao, Ogawa, Yoshihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859576/
https://www.ncbi.nlm.nih.gov/pubmed/24349208
http://dx.doi.org/10.1371/journal.pone.0082163
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author Itoh, Michiko
Kato, Hideaki
Suganami, Takayoshi
Konuma, Kuniha
Marumoto, Yoshio
Terai, Shuji
Sakugawa, Hiroshi
Kanai, Sayaka
Hamaguchi, Miho
Fukaishi, Takahiro
Aoe, Seiichiro
Akiyoshi, Kazunari
Komohara, Yoshihiro
Takeya, Motohiro
Sakaida, Isao
Ogawa, Yoshihiro
author_facet Itoh, Michiko
Kato, Hideaki
Suganami, Takayoshi
Konuma, Kuniha
Marumoto, Yoshio
Terai, Shuji
Sakugawa, Hiroshi
Kanai, Sayaka
Hamaguchi, Miho
Fukaishi, Takahiro
Aoe, Seiichiro
Akiyoshi, Kazunari
Komohara, Yoshihiro
Takeya, Motohiro
Sakaida, Isao
Ogawa, Yoshihiro
author_sort Itoh, Michiko
collection PubMed
description 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.
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spelling pubmed-38595762013-12-13 Hepatic Crown-Like Structure: A Unique Histological Feature in Non-Alcoholic Steatohepatitis in Mice and Humans Itoh, Michiko Kato, Hideaki Suganami, Takayoshi Konuma, Kuniha Marumoto, Yoshio Terai, Shuji Sakugawa, Hiroshi Kanai, Sayaka Hamaguchi, Miho Fukaishi, Takahiro Aoe, Seiichiro Akiyoshi, Kazunari Komohara, Yoshihiro Takeya, Motohiro Sakaida, Isao Ogawa, Yoshihiro PLoS One Research Article 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. Public Library of Science 2013-12-11 /pmc/articles/PMC3859576/ /pubmed/24349208 http://dx.doi.org/10.1371/journal.pone.0082163 Text en © 2013 Itoh et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Itoh, Michiko
Kato, Hideaki
Suganami, Takayoshi
Konuma, Kuniha
Marumoto, Yoshio
Terai, Shuji
Sakugawa, Hiroshi
Kanai, Sayaka
Hamaguchi, Miho
Fukaishi, Takahiro
Aoe, Seiichiro
Akiyoshi, Kazunari
Komohara, Yoshihiro
Takeya, Motohiro
Sakaida, Isao
Ogawa, Yoshihiro
Hepatic Crown-Like Structure: A Unique Histological Feature in Non-Alcoholic Steatohepatitis in Mice and Humans
title Hepatic Crown-Like Structure: A Unique Histological Feature in Non-Alcoholic Steatohepatitis in Mice and Humans
title_full Hepatic Crown-Like Structure: A Unique Histological Feature in Non-Alcoholic Steatohepatitis in Mice and Humans
title_fullStr Hepatic Crown-Like Structure: A Unique Histological Feature in Non-Alcoholic Steatohepatitis in Mice and Humans
title_full_unstemmed Hepatic Crown-Like Structure: A Unique Histological Feature in Non-Alcoholic Steatohepatitis in Mice and Humans
title_short Hepatic Crown-Like Structure: A Unique Histological Feature in Non-Alcoholic Steatohepatitis in Mice and Humans
title_sort hepatic crown-like structure: a unique histological feature in non-alcoholic steatohepatitis in mice and humans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859576/
https://www.ncbi.nlm.nih.gov/pubmed/24349208
http://dx.doi.org/10.1371/journal.pone.0082163
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