Transcriptional changes during hepatic ischemia-reperfusion in the rat.

There are few effective targeted strategies to reduce hepatic ischemia-reperfusion (IR) injury, a contributor to poor outcomes in liver transplantation recipients. It has been proposed that IR injury is driven by the generation of reactive oxygen species (ROS). However, recent studies implicate othe...

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Autores principales:	Valerie Zabala, Joan M Boylan, Paul Thevenot, Anderson Frank, Dewahar Senthoor, Varun Iyengar, Hannah Kim, Ari Cohen, Philip A Gruppuso, Jennifer A Sanders
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/12b5b00b6c6e468d98366405ff82160d
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spelling	oai:doaj.org-article:12b5b00b6c6e468d98366405ff82160d2021-12-02T20:05:47ZTranscriptional changes during hepatic ischemia-reperfusion in the rat.1932-620310.1371/journal.pone.0227038https://doaj.org/article/12b5b00b6c6e468d98366405ff82160d2019-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0227038https://doaj.org/toc/1932-6203There are few effective targeted strategies to reduce hepatic ischemia-reperfusion (IR) injury, a contributor to poor outcomes in liver transplantation recipients. It has been proposed that IR injury is driven by the generation of reactive oxygen species (ROS). However, recent studies implicate other mediators of the injury response, including mitochondrial metabolic dysfunction. We examined changes in global gene expression after transient hepatic ischemia and at several early reperfusion times to identify potential targets that could be used to protect against IR injury. Male Wistar rats were subjected to 30 minutes of 70% partial warm ischemia followed by 0, 0.5, 2, or 6 hours of reperfusion. RNA was extracted from the reperfused and non-ischemic lobes at each time point for microarray analysis. Identification of differentially expressed genes and pathway analysis were used to characterize IR-induced changes in the hepatic transcriptome. Changes in the reperfused lobes were specific to the various reperfusion times. We made the unexpected observation that many of these changes were also present in tissue from the paired non-ischemic lobes. However, the earliest reperfusion time, 30 minutes, showed a marked increase in the expression of a set of immediate-early genes (c-Fos, c-Jun, Atf3, Egr1) that was exclusive to the reperfused lobe. We interpreted these results as indicating that this early response represented a tissue autonomous response to reperfusion. In contrast, the changes that occurred in both the reperfused and non-ischemic lobes were interpreted as indicating a non-autonomous response resulting from hemodynamic changes and/or circulating factors. These tissue autonomous and non-autonomous responses may serve as targets to ameliorate IR injury.Valerie ZabalaJoan M BoylanPaul ThevenotAnderson FrankDewahar SenthoorVarun IyengarHannah KimAri CohenPhilip A GruppusoJennifer A SandersPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 14, Iss 12, p e0227038 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Valerie Zabala Joan M Boylan Paul Thevenot Anderson Frank Dewahar Senthoor Varun Iyengar Hannah Kim Ari Cohen Philip A Gruppuso Jennifer A Sanders Transcriptional changes during hepatic ischemia-reperfusion in the rat.
description	There are few effective targeted strategies to reduce hepatic ischemia-reperfusion (IR) injury, a contributor to poor outcomes in liver transplantation recipients. It has been proposed that IR injury is driven by the generation of reactive oxygen species (ROS). However, recent studies implicate other mediators of the injury response, including mitochondrial metabolic dysfunction. We examined changes in global gene expression after transient hepatic ischemia and at several early reperfusion times to identify potential targets that could be used to protect against IR injury. Male Wistar rats were subjected to 30 minutes of 70% partial warm ischemia followed by 0, 0.5, 2, or 6 hours of reperfusion. RNA was extracted from the reperfused and non-ischemic lobes at each time point for microarray analysis. Identification of differentially expressed genes and pathway analysis were used to characterize IR-induced changes in the hepatic transcriptome. Changes in the reperfused lobes were specific to the various reperfusion times. We made the unexpected observation that many of these changes were also present in tissue from the paired non-ischemic lobes. However, the earliest reperfusion time, 30 minutes, showed a marked increase in the expression of a set of immediate-early genes (c-Fos, c-Jun, Atf3, Egr1) that was exclusive to the reperfused lobe. We interpreted these results as indicating that this early response represented a tissue autonomous response to reperfusion. In contrast, the changes that occurred in both the reperfused and non-ischemic lobes were interpreted as indicating a non-autonomous response resulting from hemodynamic changes and/or circulating factors. These tissue autonomous and non-autonomous responses may serve as targets to ameliorate IR injury.
format	article
author	Valerie Zabala Joan M Boylan Paul Thevenot Anderson Frank Dewahar Senthoor Varun Iyengar Hannah Kim Ari Cohen Philip A Gruppuso Jennifer A Sanders
author_facet	Valerie Zabala Joan M Boylan Paul Thevenot Anderson Frank Dewahar Senthoor Varun Iyengar Hannah Kim Ari Cohen Philip A Gruppuso Jennifer A Sanders
author_sort	Valerie Zabala
title	Transcriptional changes during hepatic ischemia-reperfusion in the rat.
title_short	Transcriptional changes during hepatic ischemia-reperfusion in the rat.
title_full	Transcriptional changes during hepatic ischemia-reperfusion in the rat.
title_fullStr	Transcriptional changes during hepatic ischemia-reperfusion in the rat.
title_full_unstemmed	Transcriptional changes during hepatic ischemia-reperfusion in the rat.
title_sort	transcriptional changes during hepatic ischemia-reperfusion in the rat.
publisher	Public Library of Science (PLoS)
publishDate	2019
url	https://doaj.org/article/12b5b00b6c6e468d98366405ff82160d
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Transcriptional changes during hepatic ischemia-reperfusion in the rat.

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