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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6514566 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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