PloS one, 2013-12, Vol.8 (12), p.e82163-e82163
2013
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- Autor(en) / Beteiligte
- Titel
- Hepatic crown-like structure: a unique histological feature in non-alcoholic steatohepatitis in mice and humans
- Ist Teil von
- PloS one, 2013-12, Vol.8 (12), p.e82163-e82163
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0082163Titel-ID: cdi_plos_journals_1467274449
- Format
- –
- Schlagworte
- Adipocytes, Adipose tissue, Analysis, Animals, Bisphosphonates, CD11c antigen, Chronic Disease, Clodronic acid, Clodronic Acid - pharmacology, Collagen, Cytokines, Diet, Endocrinology, Fatty liver, Fatty Liver - pathology, Female, Fibroblasts, Fibrosis, Gastroenterology, Gene expression, Hepatitis, Viral, Human - pathology, Hepatocytes, Hepatology, Humans, Inflammation, Inflammation - pathology, Inflammatory diseases, Insulin resistance, Lipid Metabolism - drug effects, Lipids, Liposomes, Liposomes - metabolism, Liver, Liver - drug effects, Liver - pathology, Liver - ultrastructure, Liver cancer, Liver Cirrhosis - pathology, Liver diseases, Macrophages, Macrophages - drug effects, Macrophages - pathology, Male, Melanocortin, Metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Non-alcoholic Fatty Liver Disease, Obesity, Pathogenesis, Pathology, Phenotype, Receptor, Melanocortin, Type 4 - metabolism, Rodents, Steatosis, Tissue analysis, Type 2 diabetes, University graduates