Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin

被引：443

作者：

Kamada, Y ^{[1
]}

Tamura, S ^{[1
]}

Kiso, S ^{[1
]}

Matsumoto, H ^{[1
]}

Saji, Y ^{[1
]}

Yoshida, Y ^{[1
]}

Fukui, K ^{[1
]}

Maeda, N ^{[1
]}

Nishizawa, H ^{[1
]}

Nagaretani, H ^{[1
]}

Okamoto, Y ^{[1
]}

Kihara, S ^{[1
]}

Miyagawa, J ^{[1
]}

Shinomura, Y ^{[1
]}

Funahashi, T ^{[1
]}

Matsuzawa, Y ^{[1
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Internal Med & Mol Sci, Suita, Osaka 5650871, Japan

来源：

GASTROENTEROLOGY | 2003年 / 125卷 / 06期

关键词：

D O I：

10.1053/j.gastro.2003.08.029

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background & Aims: Obesity is one of the risk factors for liver fibrosis, in which plasma adiponectin, an adipocytokine, levels are decreased. Hepatic stellate cells play central roles in liver fibrosis. When they are activated, they undergo transformation to myofibroblast-like cells. Adiponectin suppresses the proliferation and migration of vascular smooth muscle cells, whose characteristics are similar to those of hepatic stellate cells. Adiponectin could have biological significances in liver fibrosis. Methods: The role of adiponectin on liver fibrosis induced by the administration of carbon tetrachloride twice a week for 12 weeks was tested by using adiponectin-knockout mice and an adenovirus-mediated adiponectin-expression system. We also investigated the effect of adiponectin in activated hepatic stellate cells. Results: When mice were administered carbon tetrachloride (300 muL/kg body weight) twice a week for 12 weeks, knockout mice showed extensive liver fibrosis with an enhanced expression of transforming growth factor-beta1 and connective tissue growth factor compared with wild-type mice (P < 0.05). Injection of adenovirus producing adiponectin (AdADN) before carbon tetrachloride (1000 muL/kg body weight) treatment prevented liver fibrosis in wild-type mice (P < 0.001). Injection of AdADN at 6 weeks attenuated liver fibrosis even though carbon tetrachloride was given for an additional 6 weeks (total of 12 weeks). In cultured hepatic stellate cells, adiponectin suppressed platelet-derived growth factor-induced proliferation and migration and attenuated the effect of transforming growth factor-beta1 on the gene expression of transforming growth factor-beta1 and connective tissue growth factor and on nuclear translocation of Smad2. Conclusions: The findings indicate that adiponectin attenuates liver fibrosis and could be a novel approach in its prevention.

引用

页码：1796 / 1807

页数：12

共 39 条

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