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Normothermic machine perfusion attenuates hepatic ischaemia‐reperfusion injury by inhibiting CIRP‐mediated oxidative stress and mitochondrial fission
Extracellular cold‐inducible RNA‐binding protein (CIRP) is a proinflammatory mediator that aggravates ischaemia‐reperfusion injury (IRI). Normothermic machine perfusion (NMP) could effectively alleviate the IRI of the liver, but the underlying mechanism remains to be explored. We show that human DCD...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650030/ https://www.ncbi.nlm.nih.gov/pubmed/34786826 http://dx.doi.org/10.1111/jcmm.17062 |
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author | Liu, Wenyan Fan, Yang Ding, Hongfan Han, Dan Yan, Yang Wu, Rongqian Lv, Yi Zheng, Xinglong |
author_facet | Liu, Wenyan Fan, Yang Ding, Hongfan Han, Dan Yan, Yang Wu, Rongqian Lv, Yi Zheng, Xinglong |
author_sort | Liu, Wenyan |
collection | PubMed |
description | Extracellular cold‐inducible RNA‐binding protein (CIRP) is a proinflammatory mediator that aggravates ischaemia‐reperfusion injury (IRI). Normothermic machine perfusion (NMP) could effectively alleviate the IRI of the liver, but the underlying mechanism remains to be explored. We show that human DCD livers secreted a large amount of CIRP during static cold storage (CS), which is released into the circulation after reperfusion. The expression of CIRP was related to postoperative IL‐6 levels and liver function. In a rat model, the CIRP expression was upregulated during warm ischaemia and cold storage. Then, rat DCD livers were preserved using CS, hypothermic oxygenated machine perfusion (HOPE) and NMP. C23, a CIRP inhibitor, was administrated in the HOPE group. Compared with CS, NMP significantly inhibited CIRP expression and decreased oxidative stress by downregulating NADPH oxidase and upregulating UCP2. NMP markedly inhibited the mitochondrial fission‐related proteins Drp‐1 and Fis‐1. Further, NMP increased the mitochondrial biogenesis‐related protein, TFAM. NMP significantly reduced inflammatory reactions and apoptosis after reperfusion, and NMP‐preserved liver tissue had higher bile secretion and ICG metabolism compared to the CS group. Moreover, C23 administration attenuated IRI in the HOPE group. Additionally, HL‐7702 cells were stimulated with rhCIRP and C23. High rhCIRP levels increased oxidative stress and apoptosis. In summary, NMP attenuates the IRI of DCD liver by inhibiting CIRP‐mediated oxidative stress and mitochondrial fission. |
format | Online Article Text |
id | pubmed-8650030 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86500302021-12-20 Normothermic machine perfusion attenuates hepatic ischaemia‐reperfusion injury by inhibiting CIRP‐mediated oxidative stress and mitochondrial fission Liu, Wenyan Fan, Yang Ding, Hongfan Han, Dan Yan, Yang Wu, Rongqian Lv, Yi Zheng, Xinglong J Cell Mol Med Original Articles Extracellular cold‐inducible RNA‐binding protein (CIRP) is a proinflammatory mediator that aggravates ischaemia‐reperfusion injury (IRI). Normothermic machine perfusion (NMP) could effectively alleviate the IRI of the liver, but the underlying mechanism remains to be explored. We show that human DCD livers secreted a large amount of CIRP during static cold storage (CS), which is released into the circulation after reperfusion. The expression of CIRP was related to postoperative IL‐6 levels and liver function. In a rat model, the CIRP expression was upregulated during warm ischaemia and cold storage. Then, rat DCD livers were preserved using CS, hypothermic oxygenated machine perfusion (HOPE) and NMP. C23, a CIRP inhibitor, was administrated in the HOPE group. Compared with CS, NMP significantly inhibited CIRP expression and decreased oxidative stress by downregulating NADPH oxidase and upregulating UCP2. NMP markedly inhibited the mitochondrial fission‐related proteins Drp‐1 and Fis‐1. Further, NMP increased the mitochondrial biogenesis‐related protein, TFAM. NMP significantly reduced inflammatory reactions and apoptosis after reperfusion, and NMP‐preserved liver tissue had higher bile secretion and ICG metabolism compared to the CS group. Moreover, C23 administration attenuated IRI in the HOPE group. Additionally, HL‐7702 cells were stimulated with rhCIRP and C23. High rhCIRP levels increased oxidative stress and apoptosis. In summary, NMP attenuates the IRI of DCD liver by inhibiting CIRP‐mediated oxidative stress and mitochondrial fission. John Wiley and Sons Inc. 2021-11-16 2021-12 /pmc/articles/PMC8650030/ /pubmed/34786826 http://dx.doi.org/10.1111/jcmm.17062 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Liu, Wenyan Fan, Yang Ding, Hongfan Han, Dan Yan, Yang Wu, Rongqian Lv, Yi Zheng, Xinglong Normothermic machine perfusion attenuates hepatic ischaemia‐reperfusion injury by inhibiting CIRP‐mediated oxidative stress and mitochondrial fission |
title | Normothermic machine perfusion attenuates hepatic ischaemia‐reperfusion injury by inhibiting CIRP‐mediated oxidative stress and mitochondrial fission |
title_full | Normothermic machine perfusion attenuates hepatic ischaemia‐reperfusion injury by inhibiting CIRP‐mediated oxidative stress and mitochondrial fission |
title_fullStr | Normothermic machine perfusion attenuates hepatic ischaemia‐reperfusion injury by inhibiting CIRP‐mediated oxidative stress and mitochondrial fission |
title_full_unstemmed | Normothermic machine perfusion attenuates hepatic ischaemia‐reperfusion injury by inhibiting CIRP‐mediated oxidative stress and mitochondrial fission |
title_short | Normothermic machine perfusion attenuates hepatic ischaemia‐reperfusion injury by inhibiting CIRP‐mediated oxidative stress and mitochondrial fission |
title_sort | normothermic machine perfusion attenuates hepatic ischaemia‐reperfusion injury by inhibiting cirp‐mediated oxidative stress and mitochondrial fission |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650030/ https://www.ncbi.nlm.nih.gov/pubmed/34786826 http://dx.doi.org/10.1111/jcmm.17062 |
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