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Transient Expression of Reck Under Hepatic Ischemia/Reperfusion Conditions Is Associated with Mapk Signaling Pathways
In this study, we demonstrated the involvement of matrix metalloproteinases (MMPs) in hepatic ischemia/reperfusion (I/R) injury. Our aim is to evaluate the impact of reperfusion on I/R-related changes in RECK, an MMP modulator, and mitogen-activated protein kinase (MAPKs) pathways (ERK, p38, and JNK...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277810/ https://www.ncbi.nlm.nih.gov/pubmed/32403397 http://dx.doi.org/10.3390/biom10050747 |
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author | Ferrigno, Andrea Di Pasqua, Laura G. Palladini, Giuseppina Berardo, Clarissa Verta, Roberta Richelmi, Plinio Perlini, Stefano Collotta, Debora Collino, Massimo Vairetti, Mariapia |
author_facet | Ferrigno, Andrea Di Pasqua, Laura G. Palladini, Giuseppina Berardo, Clarissa Verta, Roberta Richelmi, Plinio Perlini, Stefano Collotta, Debora Collino, Massimo Vairetti, Mariapia |
author_sort | Ferrigno, Andrea |
collection | PubMed |
description | In this study, we demonstrated the involvement of matrix metalloproteinases (MMPs) in hepatic ischemia/reperfusion (I/R) injury. Our aim is to evaluate the impact of reperfusion on I/R-related changes in RECK, an MMP modulator, and mitogen-activated protein kinase (MAPKs) pathways (ERK, p38, and JNK). Male Wistar rats were either subjected to 60 min partial-hepatic ischemia or sham-operated. After a 60 min or 120 min reperfusion, liver samples were collected for analysis of MMP-2 and MMP-9 by zymography and RECK, TIMP-1, and TIMP-2 content, MAPKs activation (ERK1/2, JNK1/2, and p38), as well as iNOS and eNOS by Western blot. Serum enzymes AST, ALT, and alkaline-phosphatase were quantified. A transitory decrease in hepatic RECK and TIMPs was associated with a transitory increase in both MMP-2 and MMP-9 activity and a robust activation of ERK1/2, JNK1/2, and p38 were detected at 60 min reperfusion. Hepatic expression of iNOS was maximally upregulated at 120 min reperfusion. An increase in eNOS was detected at 120 min reperfusion. I/R evoked significant hepatic injury in a time-dependent manner. These findings provide new insights into the underlying molecular mechanisms of reperfusion in inducing hepatic injury: a transitory decrease in RECK and TIMPs and increases in both MAPK and MMP activity suggest their role as triggering factors of the organ dysfunction. |
format | Online Article Text |
id | pubmed-7277810 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72778102020-06-12 Transient Expression of Reck Under Hepatic Ischemia/Reperfusion Conditions Is Associated with Mapk Signaling Pathways Ferrigno, Andrea Di Pasqua, Laura G. Palladini, Giuseppina Berardo, Clarissa Verta, Roberta Richelmi, Plinio Perlini, Stefano Collotta, Debora Collino, Massimo Vairetti, Mariapia Biomolecules Article In this study, we demonstrated the involvement of matrix metalloproteinases (MMPs) in hepatic ischemia/reperfusion (I/R) injury. Our aim is to evaluate the impact of reperfusion on I/R-related changes in RECK, an MMP modulator, and mitogen-activated protein kinase (MAPKs) pathways (ERK, p38, and JNK). Male Wistar rats were either subjected to 60 min partial-hepatic ischemia or sham-operated. After a 60 min or 120 min reperfusion, liver samples were collected for analysis of MMP-2 and MMP-9 by zymography and RECK, TIMP-1, and TIMP-2 content, MAPKs activation (ERK1/2, JNK1/2, and p38), as well as iNOS and eNOS by Western blot. Serum enzymes AST, ALT, and alkaline-phosphatase were quantified. A transitory decrease in hepatic RECK and TIMPs was associated with a transitory increase in both MMP-2 and MMP-9 activity and a robust activation of ERK1/2, JNK1/2, and p38 were detected at 60 min reperfusion. Hepatic expression of iNOS was maximally upregulated at 120 min reperfusion. An increase in eNOS was detected at 120 min reperfusion. I/R evoked significant hepatic injury in a time-dependent manner. These findings provide new insights into the underlying molecular mechanisms of reperfusion in inducing hepatic injury: a transitory decrease in RECK and TIMPs and increases in both MAPK and MMP activity suggest their role as triggering factors of the organ dysfunction. MDPI 2020-05-11 /pmc/articles/PMC7277810/ /pubmed/32403397 http://dx.doi.org/10.3390/biom10050747 Text en © 2020 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 Ferrigno, Andrea Di Pasqua, Laura G. Palladini, Giuseppina Berardo, Clarissa Verta, Roberta Richelmi, Plinio Perlini, Stefano Collotta, Debora Collino, Massimo Vairetti, Mariapia Transient Expression of Reck Under Hepatic Ischemia/Reperfusion Conditions Is Associated with Mapk Signaling Pathways |
title | Transient Expression of Reck Under Hepatic Ischemia/Reperfusion Conditions Is Associated with Mapk Signaling Pathways |
title_full | Transient Expression of Reck Under Hepatic Ischemia/Reperfusion Conditions Is Associated with Mapk Signaling Pathways |
title_fullStr | Transient Expression of Reck Under Hepatic Ischemia/Reperfusion Conditions Is Associated with Mapk Signaling Pathways |
title_full_unstemmed | Transient Expression of Reck Under Hepatic Ischemia/Reperfusion Conditions Is Associated with Mapk Signaling Pathways |
title_short | Transient Expression of Reck Under Hepatic Ischemia/Reperfusion Conditions Is Associated with Mapk Signaling Pathways |
title_sort | transient expression of reck under hepatic ischemia/reperfusion conditions is associated with mapk signaling pathways |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277810/ https://www.ncbi.nlm.nih.gov/pubmed/32403397 http://dx.doi.org/10.3390/biom10050747 |
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