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Novel Targets and Therapeutic Strategies to Protect Against Hepatic Ischemia Reperfusion Injury
Hepatic ischemia reperfusion injury (IRI), a fascinating topic that has drawn a lot of interest in the last few years, is a major complication caused by a variety of clinical situations, such as liver transplantation, severe trauma, vascular surgery, and hemorrhagic shock. The IRI process involves a...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764312/ https://www.ncbi.nlm.nih.gov/pubmed/35059411 http://dx.doi.org/10.3389/fmed.2021.757336 |
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author | Mao, Xin-li Cai, Yue Chen, Ya-hong Wang, Yi Jiang, Xiu-xiu Ye, Li-ping Li, Shao-wei |
author_facet | Mao, Xin-li Cai, Yue Chen, Ya-hong Wang, Yi Jiang, Xiu-xiu Ye, Li-ping Li, Shao-wei |
author_sort | Mao, Xin-li |
collection | PubMed |
description | Hepatic ischemia reperfusion injury (IRI), a fascinating topic that has drawn a lot of interest in the last few years, is a major complication caused by a variety of clinical situations, such as liver transplantation, severe trauma, vascular surgery, and hemorrhagic shock. The IRI process involves a series of complex events, including mitochondrial deenergization, metabolic acidosis, adenosine-5'-triphosphate depletion, Kupffer cell activation, calcium overload, oxidative stress, and the upregulation of pro-inflammatory cytokine signal transduction. A number of protective strategies have been reported to ameliorate IRI, including pharmacological therapy, ischemic pre-conditioning, ischemic post-conditioning, and machine reperfusion. However, most of these strategies are only at the stage of animal model research at present, and the potential mechanisms and exact therapeutic targets have yet to be clarified. IRI remains a main cause of postoperative liver dysfunction, often leading to postoperative morbidity or even mortality. Very recently, it was reported that the activation of peroxisome proliferator-activated receptor γ (PPARγ), a member of a superfamily of nuclear transcription factors activated by agonists, can attenuate IRI in the liver, and FAM3A has been confirmed to mediate the protective effect of PPARγ in hepatic IRI. In addition, non-coding RNAs, like LncRNAs and miRNAs, have also been reported to play a pivotal role in the liver IRI process. In this review, we presented an overview of the latest advances of treatment strategies and proposed potential mechanisms behind liver IRI. We also highlighted the role of several important molecules (PPARγ, FAM3A, and non-coding RNAs) in protecting against hepatic IRI. Only after achieving a comprehensive understanding of potential mechanisms and targets behind IRI can we effectively ameliorate IRI in the liver and achieve better therapeutic effects. |
format | Online Article Text |
id | pubmed-8764312 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87643122022-01-19 Novel Targets and Therapeutic Strategies to Protect Against Hepatic Ischemia Reperfusion Injury Mao, Xin-li Cai, Yue Chen, Ya-hong Wang, Yi Jiang, Xiu-xiu Ye, Li-ping Li, Shao-wei Front Med (Lausanne) Medicine Hepatic ischemia reperfusion injury (IRI), a fascinating topic that has drawn a lot of interest in the last few years, is a major complication caused by a variety of clinical situations, such as liver transplantation, severe trauma, vascular surgery, and hemorrhagic shock. The IRI process involves a series of complex events, including mitochondrial deenergization, metabolic acidosis, adenosine-5'-triphosphate depletion, Kupffer cell activation, calcium overload, oxidative stress, and the upregulation of pro-inflammatory cytokine signal transduction. A number of protective strategies have been reported to ameliorate IRI, including pharmacological therapy, ischemic pre-conditioning, ischemic post-conditioning, and machine reperfusion. However, most of these strategies are only at the stage of animal model research at present, and the potential mechanisms and exact therapeutic targets have yet to be clarified. IRI remains a main cause of postoperative liver dysfunction, often leading to postoperative morbidity or even mortality. Very recently, it was reported that the activation of peroxisome proliferator-activated receptor γ (PPARγ), a member of a superfamily of nuclear transcription factors activated by agonists, can attenuate IRI in the liver, and FAM3A has been confirmed to mediate the protective effect of PPARγ in hepatic IRI. In addition, non-coding RNAs, like LncRNAs and miRNAs, have also been reported to play a pivotal role in the liver IRI process. In this review, we presented an overview of the latest advances of treatment strategies and proposed potential mechanisms behind liver IRI. We also highlighted the role of several important molecules (PPARγ, FAM3A, and non-coding RNAs) in protecting against hepatic IRI. Only after achieving a comprehensive understanding of potential mechanisms and targets behind IRI can we effectively ameliorate IRI in the liver and achieve better therapeutic effects. Frontiers Media S.A. 2022-01-04 /pmc/articles/PMC8764312/ /pubmed/35059411 http://dx.doi.org/10.3389/fmed.2021.757336 Text en Copyright © 2022 Mao, Cai, Chen, Wang, Jiang, Ye and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Medicine Mao, Xin-li Cai, Yue Chen, Ya-hong Wang, Yi Jiang, Xiu-xiu Ye, Li-ping Li, Shao-wei Novel Targets and Therapeutic Strategies to Protect Against Hepatic Ischemia Reperfusion Injury |
title | Novel Targets and Therapeutic Strategies to Protect Against Hepatic Ischemia Reperfusion Injury |
title_full | Novel Targets and Therapeutic Strategies to Protect Against Hepatic Ischemia Reperfusion Injury |
title_fullStr | Novel Targets and Therapeutic Strategies to Protect Against Hepatic Ischemia Reperfusion Injury |
title_full_unstemmed | Novel Targets and Therapeutic Strategies to Protect Against Hepatic Ischemia Reperfusion Injury |
title_short | Novel Targets and Therapeutic Strategies to Protect Against Hepatic Ischemia Reperfusion Injury |
title_sort | novel targets and therapeutic strategies to protect against hepatic ischemia reperfusion injury |
topic | Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764312/ https://www.ncbi.nlm.nih.gov/pubmed/35059411 http://dx.doi.org/10.3389/fmed.2021.757336 |
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