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SOCS1 Is a Suppressor of Liver Fibrosis and Hepatitis-induced Carcinogenesis

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 be...

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Autores principales: Yoshida, Takafumi, Ogata, Hisanobu, Kamio, Masaki, Joo, Akiko, Shiraishi, Hiroshi, Tokunaga, Yoko, Sata, Michio, Nagai, Hisaki, Yoshimura, Akihiko
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212816/
https://www.ncbi.nlm.nih.gov/pubmed/15197228
http://dx.doi.org/10.1084/jem.20031675
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author Yoshida, Takafumi
Ogata, Hisanobu
Kamio, Masaki
Joo, Akiko
Shiraishi, Hiroshi
Tokunaga, Yoko
Sata, Michio
Nagai, Hisaki
Yoshimura, Akihiko
author_facet Yoshida, Takafumi
Ogata, Hisanobu
Kamio, Masaki
Joo, Akiko
Shiraishi, Hiroshi
Tokunaga, Yoko
Sata, Michio
Nagai, Hisaki
Yoshimura, Akihiko
author_sort Yoshida, Takafumi
collection PubMed
description 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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spelling pubmed-22128162008-03-11 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 J Exp Med Article 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. The Rockefeller University Press 2004-06-21 /pmc/articles/PMC2212816/ /pubmed/15197228 http://dx.doi.org/10.1084/jem.20031675 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
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
title SOCS1 Is a Suppressor of Liver Fibrosis and Hepatitis-induced Carcinogenesis
title_full SOCS1 Is a Suppressor of Liver Fibrosis and Hepatitis-induced Carcinogenesis
title_fullStr SOCS1 Is a Suppressor of Liver Fibrosis and Hepatitis-induced Carcinogenesis
title_full_unstemmed SOCS1 Is a Suppressor of Liver Fibrosis and Hepatitis-induced Carcinogenesis
title_short SOCS1 Is a Suppressor of Liver Fibrosis and Hepatitis-induced Carcinogenesis
title_sort socs1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212816/
https://www.ncbi.nlm.nih.gov/pubmed/15197228
http://dx.doi.org/10.1084/jem.20031675
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