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

研究成果: Article

128 引用 (Scopus)

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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.

元の言語English
ページ(範囲)1701-1707
ページ数7
ジャーナルJournal of Experimental Medicine
199
発行部数12
DOI
出版物ステータスPublished - 2004 6 21
外部発表Yes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

これを引用

Yoshida, T., Ogata, H., Kamio, M., Joo, A., Shiraishi, H., Tokunaga, Y., Sata, M., Nagai, H., & Yoshimura, A. (2004). SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis. Journal of Experimental Medicine, 199(12), 1701-1707. https://doi.org/10.1084/jem.20031675