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Anti-Apoptotic Effects of Recombinant Human Hepatocyte Growth Factor on Hepatocytes Were Associated with Intrahepatic Hemorrhage Suppression Indicated by the Preservation of Prothrombin Time

Hepatocyte growth factor (HGF) is an endogenously expressed bioactive substance that has a strong anti-apoptotic effect. In this study, we biochemically and histologically characterized the effects of rh-HGF on in vitro human hepatocyte injury and mouse acute liver failure (ALF) models, both of whic...

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Autores principales: Motoi, Sotaro, Toyoda, Hiroko, Obara, Takashi, Ohta, Etsuko, Arita, Yoshihisa, Negishi, Kana, Moriya, Katsuhiro, Kuboi, Yoshikazu, Soejima, Motohiro, Imai, Toshio, Ido, Akio, Tsubouchi, Hirohito, Kawano, Tetsu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514566/
https://www.ncbi.nlm.nih.gov/pubmed/31013780
http://dx.doi.org/10.3390/ijms20081821
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author Motoi, Sotaro
Toyoda, Hiroko
Obara, Takashi
Ohta, Etsuko
Arita, Yoshihisa
Negishi, Kana
Moriya, Katsuhiro
Kuboi, Yoshikazu
Soejima, Motohiro
Imai, Toshio
Ido, Akio
Tsubouchi, Hirohito
Kawano, Tetsu
author_facet Motoi, Sotaro
Toyoda, Hiroko
Obara, Takashi
Ohta, Etsuko
Arita, Yoshihisa
Negishi, Kana
Moriya, Katsuhiro
Kuboi, Yoshikazu
Soejima, Motohiro
Imai, Toshio
Ido, Akio
Tsubouchi, Hirohito
Kawano, Tetsu
author_sort Motoi, Sotaro
collection PubMed
description Hepatocyte growth factor (HGF) is an endogenously expressed bioactive substance that has a strong anti-apoptotic effect. In this study, we biochemically and histologically characterized the effects of rh-HGF on in vitro human hepatocyte injury and mouse acute liver failure (ALF) models, both of which were induced by antibody-mediated Fas signaling. rh-HGF inhibited intracellular caspase-3/7 activation and cytokeratin 18 (CK-18) fragment release in both models. Histologically, rh-HGF dramatically suppressed parenchymal damage and intrahepatic hemorrhage. Among the laboratory parameters, prothrombin time (PT) was strongly preserved by rh-HGF, and PT was well correlated with the degree of intrahepatic hemorrhage. These results showed that the anti-apoptotic effect of rh-HGF on hepatocytes coincided strikingly with the suppression of intrahepatic hemorrhage. PT was considered to be the best parameter that correlated with the intrahepatic hemorrhages associated with hepatocellular damage. The action of rh-HGF might derive not only from its anti-apoptosis effects on liver parenchymal cells but also from its stabilization of structural and vasculature integrity.
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spelling pubmed-65145662019-05-30 Anti-Apoptotic Effects of Recombinant Human Hepatocyte Growth Factor on Hepatocytes Were Associated with Intrahepatic Hemorrhage Suppression Indicated by the Preservation of Prothrombin Time Motoi, Sotaro Toyoda, Hiroko Obara, Takashi Ohta, Etsuko Arita, Yoshihisa Negishi, Kana Moriya, Katsuhiro Kuboi, Yoshikazu Soejima, Motohiro Imai, Toshio Ido, Akio Tsubouchi, Hirohito Kawano, Tetsu Int J Mol Sci Article Hepatocyte growth factor (HGF) is an endogenously expressed bioactive substance that has a strong anti-apoptotic effect. In this study, we biochemically and histologically characterized the effects of rh-HGF on in vitro human hepatocyte injury and mouse acute liver failure (ALF) models, both of which were induced by antibody-mediated Fas signaling. rh-HGF inhibited intracellular caspase-3/7 activation and cytokeratin 18 (CK-18) fragment release in both models. Histologically, rh-HGF dramatically suppressed parenchymal damage and intrahepatic hemorrhage. Among the laboratory parameters, prothrombin time (PT) was strongly preserved by rh-HGF, and PT was well correlated with the degree of intrahepatic hemorrhage. These results showed that the anti-apoptotic effect of rh-HGF on hepatocytes coincided strikingly with the suppression of intrahepatic hemorrhage. PT was considered to be the best parameter that correlated with the intrahepatic hemorrhages associated with hepatocellular damage. The action of rh-HGF might derive not only from its anti-apoptosis effects on liver parenchymal cells but also from its stabilization of structural and vasculature integrity. MDPI 2019-04-12 /pmc/articles/PMC6514566/ /pubmed/31013780 http://dx.doi.org/10.3390/ijms20081821 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Motoi, Sotaro
Toyoda, Hiroko
Obara, Takashi
Ohta, Etsuko
Arita, Yoshihisa
Negishi, Kana
Moriya, Katsuhiro
Kuboi, Yoshikazu
Soejima, Motohiro
Imai, Toshio
Ido, Akio
Tsubouchi, Hirohito
Kawano, Tetsu
Anti-Apoptotic Effects of Recombinant Human Hepatocyte Growth Factor on Hepatocytes Were Associated with Intrahepatic Hemorrhage Suppression Indicated by the Preservation of Prothrombin Time
title Anti-Apoptotic Effects of Recombinant Human Hepatocyte Growth Factor on Hepatocytes Were Associated with Intrahepatic Hemorrhage Suppression Indicated by the Preservation of Prothrombin Time
title_full Anti-Apoptotic Effects of Recombinant Human Hepatocyte Growth Factor on Hepatocytes Were Associated with Intrahepatic Hemorrhage Suppression Indicated by the Preservation of Prothrombin Time
title_fullStr Anti-Apoptotic Effects of Recombinant Human Hepatocyte Growth Factor on Hepatocytes Were Associated with Intrahepatic Hemorrhage Suppression Indicated by the Preservation of Prothrombin Time
title_full_unstemmed Anti-Apoptotic Effects of Recombinant Human Hepatocyte Growth Factor on Hepatocytes Were Associated with Intrahepatic Hemorrhage Suppression Indicated by the Preservation of Prothrombin Time
title_short Anti-Apoptotic Effects of Recombinant Human Hepatocyte Growth Factor on Hepatocytes Were Associated with Intrahepatic Hemorrhage Suppression Indicated by the Preservation of Prothrombin Time
title_sort anti-apoptotic effects of recombinant human hepatocyte growth factor on hepatocytes were associated with intrahepatic hemorrhage suppression indicated by the preservation of prothrombin time
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514566/
https://www.ncbi.nlm.nih.gov/pubmed/31013780
http://dx.doi.org/10.3390/ijms20081821
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