Mouse model of carbon tetrachloride induced liver fibrosis: Histopathological changes and expression of CD133 and epidermal growth factor.
Mouse model of carbon tetrachloride induced liver fibrosis: Histopathological changes and expression of CD133 and epidermal growth factor.
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DOI：
10.1186/1471-230x-10-79
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发表时间：
2010-07-09
影响因子：
2.4
通讯作者：
Tanabe KK
中科院分区：
文献类型：
--
作者：
Fujii T;Fuchs BC;Yamada S;Lauwers GY;Kulu Y;Goodwin JM;Lanuti M;Tanabe KK
在人类慢性肝损伤的背景下，表皮生长因子（EGF）和表皮生长因子受体（EGFR）被上调，并且已经被提出在肝再生和肝细胞癌（HCC）的发展中具有重要作用。慢性肝损伤也导致肝星状细胞（HSC）分化，并且已经在大鼠中描述了表达CD 133并表现出祖细胞性质的HSC的新亚群。四氯化碳（CCl 4）诱导的小鼠模型历来依赖于研究肝损伤和再生。我们将小鼠暴露于CCl 4以评估EGF和CD 133 + HSC在慢性损伤的肝脏中是否上调。通过经口管饲法，每周三次向A/J系小鼠给予四氯化碳橄榄油溶液。CCl 4处理15周后，在所有肝脏中发现了多个分化良好的HCC。值得注意的是，HCC是在纤维化而不是肝硬化的背景下发展的。CCl 4处理后，CD 133显著上调，还观察到HSC的代表性标志物结蛋白和胶质细胞酸性蛋白的表达增加。EGF的表达显着下降，相反，在人类中的观察，而双调蛋白，另一种EGFR配体的表达显着增加。慢性肝病的组织病理学和分子发病机制存在种属特异性差异。CCl 4诱导的A/J小鼠慢性肝损伤与导致HCC的人类肝硬化相比具有重要差异。
In the setting of chronic liver injury in humans, epidermal growth factor (EGF) and EGF receptor (EGFR) are up-regulated and have been proposed to have vital roles in both liver regeneration and development of hepatocellular carcinoma (HCC). Chronic liver injury also leads to hepatic stellate cell (HSC) differentiation and a novel subpopulation of HSCs which express CD133 and exhibit properties of progenitor cells has been described in rats. The carbon tetrachloride (CCl4)-induced mouse model has been historically relied upon to study liver injury and regeneration. We exposed mice to CCl4 to assess whether EGF and CD133+ HSCs are up-regulated in chronically injured liver. CCl4 in olive oil was administered to strain A/J mice three times per week by oral gavage. Multiple well-differentiated HCCs were found in all livers after 15 weeks of CCl4 treatment. Notably, HCCs developed within the setting of fibrosis and not cirrhosis. CD133 was dramatically up-regulated after CCl4 treatment, and increased expression of desmin and glial fibrillary acidic protein, representative markers of HSCs, was also observed. EGF expression significantly decreased, contrary to observations in humans, whereas the expression of amphiregulin, another EGFR ligand, was significantly increased. Species-specific differences exist with respect to the histopathological and molecular pathogenesis of chronic liver disease. CCl4-induced chronic liver injury in A/J mice has important differences compared to human cirrhosis leading to HCC.