Hepatic crown-like structure: a unique histological feature in non-alcoholic steatohepatitis in mice and humans.
Hepatic crown-like structure: a unique histological feature in non-alcoholic steatohepatitis in mice and humans.
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肝冠状结构：小鼠和人类非酒精性脂肪性肝炎的独特组织学特征。
DOI：
10.1371/journal.pone.0082163
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ogawa Y
中科院分区：
文献类型：
--
作者：
Itoh M;Kato H;Suganami T;Konuma K;Marumoto Y;Terai S;Sakugawa H;Kanai S;Hamaguchi M;Fukaishi T;Aoe S;Akiyoshi K;Komohara Y;Takeya M;Sakaida I;Ogawa Y
尽管巨噬细胞被认为对于慢性炎症性疾病的发病机制至关重要，但它们如何参与从简单脂肪变性到非酒精性脂肪性肝炎（NASH）的疾病进展却知之甚少。在这里，我们报告了人类 NASH 小鼠模型中独特的组织学结构，称为“肝冠样结构（hCLS）”；黑皮质素 4 受体缺陷小鼠采用西方饮食喂养。在 hCLS 中，CD11c 阳性巨噬细胞聚集，以大脂滴包围肝细胞，这与肥胖脂肪组织中描述的类似。组织学分析表明，hCLS 与成纤维细胞活化和胶原沉积密切相关。当氯膦酸盐脂质体治疗有效地消耗分散在肝脏中的巨噬细胞时，hCLS中的巨噬细胞保持完整，肝脏炎症和纤维化基因的表达不受影响，这表明hCLS是NASH进展过程中炎症和纤维化的重要来源。值得注意的是，hCLS的数量与肝纤维化的程度呈正相关。我们还观察到非酒精性脂肪肝/NASH 患者肝脏中 hCLS 数量增加。总的来说，我们的数据提供了 hCLS 参与肝脏炎症和纤维化发展的证据，从而表明其在从简单脂肪变性到 NASH 的疾病进展中的病理生理学作用。
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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DOI：
10.1002/cne.22221
发表时间：
2010-01-01
期刊：
The Journal of comparative neurology
影响因子：
--
作者：
Gautron L;Lee C;Funahashi H;Friedman J;Lee S;Elmquist J
通讯作者：
Elmquist J
影响因子：
5.8
作者：
Bremer, Andrew A.;Devaraj, Sridevi;Jialal, Ishwarlal
通讯作者：
Jialal, Ishwarlal
影响因子：
2.2
作者：
Fotiadu, Anastasia;Gagalis, Asterios;Hytiroglou, Prodromos
通讯作者：
Hytiroglou, Prodromos
DOI：
10.1161/atvbaha.106.136853
发表时间：
2007-09-01
影响因子：
8.7
作者：
Itoh, Michiko;Suganami, Takayoshi;Ogawa, Yoshihiro
通讯作者：
Ogawa, Yoshihiro
影响因子：
29.4
作者：
Kamada, Y;Tamura, S;Matsuzawa, Y
通讯作者：
Matsuzawa, Y