Altered liver gene expression in CCl4-cirrhotic rats is partially normalized by insulin-like growth factor-I
Altered liver gene expression in CCl4-cirrhotic rats is partially normalized by insulin-like growth factor-I
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DOI：
10.1016/s1357-2725(01)00123-6
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发表时间：
2002-03-01
影响因子：
4
通讯作者：
Avila, MA
中科院分区：
文献类型：
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作者：
Mirpuri, E;García-Trevijano, ER;Avila, MA
我们之前已经证明，给 CC4 肝硬化大鼠施用低剂量的胰岛素样生长因子-I (IGF-I) 可改善肝功能并减少纤维化。为了更好地了解 IGF-I 的保肝作用背后的机制，并鉴定那些在肝硬化和 IGF-I 治疗后表达受到影响的基因，我们通过聚合酶链反应 (PCR) 对对照大鼠和接受或未接受 IGF-I 治疗的 CC14 肝硬化大鼠的肝脏进行了 mRNA 分析的差异显示。我们已经鉴定出 16 个在肝硬化肝脏中上调或下调的基因。 IGF-I 治疗使其中 8 个基因的表达部分正常化，包括丝氨酸蛋白酶抑制剂，如 serpin-2 和 alpha-1-antichyniotripsin、alpha-1-酸性糖蛋白和 alpha-2u-球蛋白。此外，我们还发现 IGF-I 增强了肝硬化肝脏的再生活性，这通过增殖细胞核抗原 (PCNA) 表达的增加来确定。最后，IGF-I 治疗部分恢复了生长激素受体 (GHR) 的表达和整体基因组 DNA 甲基化水平，这些水平在人类和实验性肝硬化中降低。综上所述，我们的观察证实了 IGF-I 的保肝作用，并表明这种作用可以部分通过肝脏基因表达、生长激素 (GH) 反应性和整体基因组 DNA 甲基化的正常化来发挥。 (C) 2002 Elsevier Science Ltd. 保留所有权利。
We have previously shown that the administration of low doses of insulin-like growth factor-I (IGF-I) to CC4-cirrhotic rats improves liver function and reduces fibrosis. To better understand the mechanisms behind the hepatoprotective effects of IGF-I, and to identify those genes whose expression is affected in cirrhosis and after IGF-I treatment, we have performed differential display of mRNA analysis by means of polymerase chain reaction (PCR) in livers from control and CC14-cirrhotic rats treated or not with IGF-I. We have identified 16 genes that were up- or down-regulated in the cirrhotic liver. IGF-I treatment partially normalized the expression of eight of these genes, including serine proteinase inhibitors such as serpin-2 and alpha-1-antichyniotripsin, alpha-1-acid glycoprotein, and alpha-2u-globulin. Additionally, we show that IGF-I enhanced the regenerative activity in the cirrhotic liver, as determined by the increased expression of the proliferating cell nuclear antigen (PCNA). Finally, IGF-I treatment partially restored the expression of growth hormone receptor (GHR) and the levels of global genomic DNA methylation, which are reduced in human and experimental cirrhosis. Taken together, our observations confirm the hepatoprotective effects of IGF-I, and suggest that this action can be exerted in part through the normalization of liver gene expression, growth hormone (GH) responsiveness and global genomic DNA methylation. (C) 2002 Elsevier Science Ltd. All rights reserved.