SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis.
SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis.
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DOI：
10.1084/jem.20031675
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发表时间：
2004-06-21
期刊：
影响因子：
--
通讯作者：
Yoshimura A
中科院分区：
文献类型：
--
作者：
Yoshida T;Ogata H;Kamio M;Joo A;Shiraishi H;Tokunaga Y;Sata M;Nagai H;Yoshimura A
肝细胞癌（HCC）主要由肝硬化和严重的肝纤维化发展而来，这些肝纤维化是由肝脏的长期炎症建立的。细胞因子信号传导抑制因子-1（SOCS 1）基因是细胞因子信号传导的负调节因子，其通过DNA甲基化沉默与HCC的发生或进展有关。然而，SOCS 1如何促进HCC尚不清楚。我们检测了超过200例慢性肝病患者的SOCS 1基因甲基化，发现肝纤维化的严重程度与SOCS 1基因甲基化密切相关。在使用二甲基亚硝胺的小鼠肝纤维化模型中，SOCS 1基因单倍不足的小鼠（SOCS 1 −/+小鼠）比野生型同窝小鼠（SOCS 1 +/+小鼠）发生更严重的肝纤维化。此外，SOCS 1基因的杂合缺失也增强了致癌物诱导的HCC发展。这些发现表明，SOCS 1有助于防止肝损伤和纤维化，也可能防止肝癌发生。
Hepatocellular carcinomas (HCCs) mainly develop from liver cirrhosis and severe liver fibrosis that are established with long-lasting inflammation of the liver. Silencing of the suppressor of the cytokine signaling-1 (SOCS1) gene, a negative regulator of cytokine signaling, by DNA methylation has been implicated in development or progress of HCC. However, how SOCS1 contributes to HCC is unknown. We examined SOCS1 gene methylation in >200 patients with chronic liver disease and found that the severity of liver fibrosis is strongly correlated with SOCS1 gene methylation. In murine liver fibrosis models using dimethylnitrosamine, mice with haploinsufficiency of the SOCS1 gene (SOCS1−/+ mice) developed more severe liver fibrosis than did wild-type littermates (SOCS1+/+ mice). Moreover, carcinogen-induced HCC development was also enhanced by heterozygous deletion of the SOCS1 gene. These findings suggest that SOCS1 contributes to protection against hepatic injury and fibrosis, and may also protect against hepatocarcinogenesis.
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DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
24.5
作者：
Kaneto, H;Sasaki, S;Imai, K
通讯作者：
Imai, K
影响因子：
2.6
作者：
Metcalf, D
通讯作者：
Metcalf, D
影响因子：
13.5
作者：
Bedossa, P;Poynard, T
通讯作者：
Poynard, T
影响因子：
64.5
作者：
Marine, JC;Topham, DJ;Ihle, JN
通讯作者：
Ihle, JN