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

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

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
Volume199
Issue number12
DOIs
Publication statusPublished - 2004 Jun 21
Externally publishedYes

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Liver Cirrhosis
Hepatitis
Carcinogenesis
Cytokines
Hepatocellular Carcinoma
Methylation
Genes
Suppressor Genes
Dimethylnitrosamine
Haploinsufficiency
Liver
DNA Methylation
Carcinogens
Liver Diseases
Fibrosis
Chronic Disease
Inflammation
Wounds and Injuries

Keywords

  • Cytokine
  • DNA methylation
  • Hepatitis C virus
  • STAT
  • TGF-β

ASJC Scopus subject areas

  • Immunology

Cite this

SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis. / Yoshida, Takafumi; Ogata, Hisanobu; Kamio, Masaki; Joo, Akiko; Shiraishi, Hiroshi; Tokunaga, Yoko; Sata, Michio; Nagai, Hisaki; Yoshimura, Akihiko.

In: Journal of Experimental Medicine, Vol. 199, No. 12, 21.06.2004, p. 1701-1707.

Research output: Contribution to journalArticle

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, vol. 199, no. 12, pp. 1701-1707. https://doi.org/10.1084/jem.20031675
Yoshida T, Ogata H, Kamio M, Joo A, Shiraishi H, Tokunaga Y et al. SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis. Journal of Experimental Medicine. 2004 Jun 21;199(12):1701-1707. https://doi.org/10.1084/jem.20031675
Yoshida, Takafumi ; Ogata, Hisanobu ; Kamio, Masaki ; Joo, Akiko ; Shiraishi, Hiroshi ; Tokunaga, Yoko ; Sata, Michio ; Nagai, Hisaki ; Yoshimura, Akihiko. / SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis. In: Journal of Experimental Medicine. 2004 ; Vol. 199, No. 12. pp. 1701-1707.
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