Improvement of Sepsis by Hepatocyte Growth Factor, an Anti-Inflammatory Regulator: Emerging Insights and Therapeutic Potential

Sepsis-induced multiple organ failure (MOF) is the most frequent lethal disease in intensive care units. Thus, it is important to elucidate the self-defensive mechanisms of sepsis-induced MOF. Hepatocyte growth factor (HGF) is now recognized as an organotrophic factor, which is essential for organog...

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Main Authors: Shinya Mizuno, Toshikazu Nakamura
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Gastroenterology Research and Practice
Online Access:http://dx.doi.org/10.1155/2012/909350
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author Shinya Mizuno
Toshikazu Nakamura
author_facet Shinya Mizuno
Toshikazu Nakamura
author_sort Shinya Mizuno
collection DOAJ
description Sepsis-induced multiple organ failure (MOF) is the most frequent lethal disease in intensive care units. Thus, it is important to elucidate the self-defensive mechanisms of sepsis-induced MOF. Hepatocyte growth factor (HGF) is now recognized as an organotrophic factor, which is essential for organogenesis during embryonic growth and regeneration in adulthood. HGF production is enhanced in response to infectious challenges, but the increase in endogenous HGF levels is transient and insufficient, with a time lag between tissue injuries and HGF upregulation, during progression of septic MOF. Thus, administration of active-formed HGF might be a new candidate for therapeutic development of MOF. HGF has an ability to target endotoxin-challenged macrophages and inhibits the upregulation of inflammatory cytokines through nuclear factor-κB-inactivated mechanisms. HGF also targets the endothelium and epithelium of various organs to suppress local inflammation, coagulation, and apoptotic death. This paper summarizes the novel mechanisms of HGF for attenuating sepsis-related pathological conditions with a focus on sepsis-induced MOF.
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spelling doaj-art-ce7d66c698764be8b653a3a64fd6aad22025-08-20T02:19:30ZengWileyGastroenterology Research and Practice1687-61211687-630X2012-01-01201210.1155/2012/909350909350Improvement of Sepsis by Hepatocyte Growth Factor, an Anti-Inflammatory Regulator: Emerging Insights and Therapeutic PotentialShinya Mizuno0Toshikazu Nakamura1Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2-B7 Yamadaoka, Suita 565-0871, JapanKringle Pharma Joint Research Division for Regenerative Drug Discovery, Center for Advanced Science and Innovation, Osaka University, 2-1 Yamadaoka, Suita 565-0871, JapanSepsis-induced multiple organ failure (MOF) is the most frequent lethal disease in intensive care units. Thus, it is important to elucidate the self-defensive mechanisms of sepsis-induced MOF. Hepatocyte growth factor (HGF) is now recognized as an organotrophic factor, which is essential for organogenesis during embryonic growth and regeneration in adulthood. HGF production is enhanced in response to infectious challenges, but the increase in endogenous HGF levels is transient and insufficient, with a time lag between tissue injuries and HGF upregulation, during progression of septic MOF. Thus, administration of active-formed HGF might be a new candidate for therapeutic development of MOF. HGF has an ability to target endotoxin-challenged macrophages and inhibits the upregulation of inflammatory cytokines through nuclear factor-κB-inactivated mechanisms. HGF also targets the endothelium and epithelium of various organs to suppress local inflammation, coagulation, and apoptotic death. This paper summarizes the novel mechanisms of HGF for attenuating sepsis-related pathological conditions with a focus on sepsis-induced MOF.http://dx.doi.org/10.1155/2012/909350
spellingShingle Shinya Mizuno
Toshikazu Nakamura
Improvement of Sepsis by Hepatocyte Growth Factor, an Anti-Inflammatory Regulator: Emerging Insights and Therapeutic Potential
Gastroenterology Research and Practice
title Improvement of Sepsis by Hepatocyte Growth Factor, an Anti-Inflammatory Regulator: Emerging Insights and Therapeutic Potential
title_full Improvement of Sepsis by Hepatocyte Growth Factor, an Anti-Inflammatory Regulator: Emerging Insights and Therapeutic Potential
title_fullStr Improvement of Sepsis by Hepatocyte Growth Factor, an Anti-Inflammatory Regulator: Emerging Insights and Therapeutic Potential
title_full_unstemmed Improvement of Sepsis by Hepatocyte Growth Factor, an Anti-Inflammatory Regulator: Emerging Insights and Therapeutic Potential
title_short Improvement of Sepsis by Hepatocyte Growth Factor, an Anti-Inflammatory Regulator: Emerging Insights and Therapeutic Potential
title_sort improvement of sepsis by hepatocyte growth factor an anti inflammatory regulator emerging insights and therapeutic potential
url http://dx.doi.org/10.1155/2012/909350
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