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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...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2004
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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. |
format | Text |
id | pubmed-2212816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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