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Regulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3

Suppressor of cytokine signaling 3 (SOCS3) down-regulates several signaling pathways in multiple cell types, and previous data suggest that SOCS3 may shut off cytokine activation at the early stages of liver regeneration (Campbell, J.S., L. Prichard, F. Schaper, J. Schmitz, A. Stephenson-Famy, M.E....

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Autores principales: Riehle, Kimberly J., Campbell, Jean S., McMahan, Ryan S., Johnson, Melissa M., Beyer, Richard P., Bammler, Theo K., Fausto, Nelson
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234364/
https://www.ncbi.nlm.nih.gov/pubmed/18158318
http://dx.doi.org/10.1084/jem.20070820
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author Riehle, Kimberly J.
Campbell, Jean S.
McMahan, Ryan S.
Johnson, Melissa M.
Beyer, Richard P.
Bammler, Theo K.
Fausto, Nelson
author_facet Riehle, Kimberly J.
Campbell, Jean S.
McMahan, Ryan S.
Johnson, Melissa M.
Beyer, Richard P.
Bammler, Theo K.
Fausto, Nelson
author_sort Riehle, Kimberly J.
collection PubMed
description Suppressor of cytokine signaling 3 (SOCS3) down-regulates several signaling pathways in multiple cell types, and previous data suggest that SOCS3 may shut off cytokine activation at the early stages of liver regeneration (Campbell, J.S., L. Prichard, F. Schaper, J. Schmitz, A. Stephenson-Famy, M.E. Rosenfeld, G.M. Argast, P.C. Heinrich, and N. Fausto. 2001.J. Clin. Invest. 107:1285–1292). We developed Socs3 hepatocyte-specific knockout (Socs3 h-KO) mice to directly study the role of SOCS3 during liver regeneration after a two-thirds partial hepatectomy (PH). Socs3 h-KO mice demonstrate marked enhancement of DNA replication and liver weight restoration after PH in comparison with littermate controls. Without SOCS3, signal transducer and activator of transcription 3 (STAT3) phosphorylation is prolonged, and activation of the mitogenic extracellular signal-regulated kinase 1/2 (ERK1/2) is enhanced after PH. In vitro, we show that SOCS3 deficiency enhances hepatocyte proliferation in association with enhanced STAT3 and ERK activation after epidermal growth factor or interleukin 6 stimulation. Microarray analyses show that SOCS3 modulates a distinct set of genes, which fall into diverse physiological categories, after PH. Using a model of chemical-induced carcinogenesis, we found that Socs3 h-KO mice develop hepatocellular carcinoma at an accelerated rate. By acting on cytokines and multiple proliferative pathways, SOCS3 modulates both physiological and neoplastic proliferative processes in the liver and may act as a tumor suppressor.
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spelling pubmed-22343642008-07-21 Regulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3 Riehle, Kimberly J. Campbell, Jean S. McMahan, Ryan S. Johnson, Melissa M. Beyer, Richard P. Bammler, Theo K. Fausto, Nelson J Exp Med Articles Suppressor of cytokine signaling 3 (SOCS3) down-regulates several signaling pathways in multiple cell types, and previous data suggest that SOCS3 may shut off cytokine activation at the early stages of liver regeneration (Campbell, J.S., L. Prichard, F. Schaper, J. Schmitz, A. Stephenson-Famy, M.E. Rosenfeld, G.M. Argast, P.C. Heinrich, and N. Fausto. 2001.J. Clin. Invest. 107:1285–1292). We developed Socs3 hepatocyte-specific knockout (Socs3 h-KO) mice to directly study the role of SOCS3 during liver regeneration after a two-thirds partial hepatectomy (PH). Socs3 h-KO mice demonstrate marked enhancement of DNA replication and liver weight restoration after PH in comparison with littermate controls. Without SOCS3, signal transducer and activator of transcription 3 (STAT3) phosphorylation is prolonged, and activation of the mitogenic extracellular signal-regulated kinase 1/2 (ERK1/2) is enhanced after PH. In vitro, we show that SOCS3 deficiency enhances hepatocyte proliferation in association with enhanced STAT3 and ERK activation after epidermal growth factor or interleukin 6 stimulation. Microarray analyses show that SOCS3 modulates a distinct set of genes, which fall into diverse physiological categories, after PH. Using a model of chemical-induced carcinogenesis, we found that Socs3 h-KO mice develop hepatocellular carcinoma at an accelerated rate. By acting on cytokines and multiple proliferative pathways, SOCS3 modulates both physiological and neoplastic proliferative processes in the liver and may act as a tumor suppressor. The Rockefeller University Press 2008-01-21 /pmc/articles/PMC2234364/ /pubmed/18158318 http://dx.doi.org/10.1084/jem.20070820 Text en Copyright © 2008, 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 Articles
Riehle, Kimberly J.
Campbell, Jean S.
McMahan, Ryan S.
Johnson, Melissa M.
Beyer, Richard P.
Bammler, Theo K.
Fausto, Nelson
Regulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3
title Regulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3
title_full Regulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3
title_fullStr Regulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3
title_full_unstemmed Regulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3
title_short Regulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3
title_sort regulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234364/
https://www.ncbi.nlm.nih.gov/pubmed/18158318
http://dx.doi.org/10.1084/jem.20070820
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