SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis

Takafumi Yoshida, Hisanobu Ogata, Masaki Kamio, Akiko Joo, Hiroshi Shiraishi, Yoko Tokunaga, Michio Sata, Hisaki Nagai, Akihiko Yoshimura

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154 Citations (Scopus)


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 SO CS1 gene. These findings suggest that SOCS1 contributes to protection against hepatic injury and fibrosis, and may also protect against hepatocarcinogenesis.

Original languageEnglish
Pages (from-to)1701-1707
Number of pages7
JournalJournal of Experimental Medicine
Issue number12
Publication statusPublished - Jun 21 2004

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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