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KMID : 0613820150250040463
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Journal of Life Science
2015 Volume.25 No. 4 p.463 ~ p.472
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Adrenomedullin Deficiency Increases the Susceptibility of Liver Fibrosis Induced by CCl4
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Ji Ae-Ri
Hwang Mee-Yul
Kim Ah-Young
Lee Eun-Mi
Lee Eun-Joo
Lee Myeong-Mi
Sung Soo-Eun
Kim Sang-Hyeob
Park Jin-Kyu
Jeong Kyu-Shik
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Abstract
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Adrenomedullin (AM) is a peptide expressed in all body tissues, and its related receptors are increased in liver fibrosis. In this study, we evaluated the effect of AM deficiency on liver fibrogenesis induced by CCl4 using AM heterozygous (HT) mice. The animals received a single injection of CCl4 or olive oil for the acute experiment, and received CCl4 or olive oil three times a week for 6 weeks for the chronic experiment. Fibrosis was accessed using histopathological analysis and the western blot. The AM HT mice showed mild pericentrilobular degeneration when compared to the AM wild type (WT) mice. In the acute experiment, there was no significant difference between the AM WT and AM HT mice. However, in the chronic experiment, the CCl4-treated AM HT mice showed more severe liver fibrosis than that of the CCl4-treated AM WT mice. The AST and ALT levels of the AM HT CCl4 group were higher than those of the AM WT CCl4 group. Additionally, the collagen deposition, α- SMA protein and TGF-β protein were increased in the AM HT CCl4 group when compared to the AM WT CCl4 group. The AM HT mice also exhibited severe lipid peroxidation through the GSH decrement. Taken together, our data suggest that AM deficiency increases the susceptibility to liver fibrosis induced by CCl4, indicating a novel therapeutic target for patients with liver fibrosis.
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KEYWORD
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Adrenomedullin, lipid peroxidation, liver fibrosis, TGF-β
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