Determination of a microRNA signature of protective kidney ischemic preconditioning originating from proximal tubules

Abstract Ischemic preconditioning (IPC) is effective in limiting subsequent ischemic acute kidney injury in experimental models. MicroRNAs are an important class of post-transcriptional regulator and show promise as biomarkers of kidney injury. We evaluated the time- and dose-dependence of benefit f...

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Autores principales:	Usman Khalid, Robert H. Jenkins, Robert Andrews, Gilda Pino-Chavez, Benjamin C. Cossins, Rafael Chavez, Timothy Bowen, Donald J. Fraser
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f300b59f825445b7aca92d3fdb870348
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spelling	oai:doaj.org-article:f300b59f825445b7aca92d3fdb8703482021-12-02T14:35:47ZDetermination of a microRNA signature of protective kidney ischemic preconditioning originating from proximal tubules10.1038/s41598-021-89195-32045-2322https://doaj.org/article/f300b59f825445b7aca92d3fdb8703482021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89195-3https://doaj.org/toc/2045-2322Abstract Ischemic preconditioning (IPC) is effective in limiting subsequent ischemic acute kidney injury in experimental models. MicroRNAs are an important class of post-transcriptional regulator and show promise as biomarkers of kidney injury. We evaluated the time- and dose-dependence of benefit from IPC in a rat model of functional (bilateral) ischemia–reperfusion injury (IRI). We found optimal protection from subsequent injury following short, repetitive sequences of preconditioning insult. We subsequently used hybridization array and microRNA sequencing to characterize microRNA signatures of protective IPC and of IRI. These approaches identified a profile of microRNA changes consequent on IRI, that were limited by prior IPC. To localize these signals within the kidney, we used laser capture microdissection and RT-qPCR to measure microRNA abundance in nephron segments, pinpointing microRNA changes principally to glomeruli and proximal tubules. Our data describe a unique microRNA signature for IRI in the rat kidney. Pulsatile IPC reduces kidney damage following IRI and diminishes this microRNA signal. We have also identified candidate microRNAs that may act as biomarkers of injury and therapeutic targets in this context.Usman KhalidRobert H. JenkinsRobert AndrewsGilda Pino-ChavezBenjamin C. CossinsRafael ChavezTimothy BowenDonald J. FraserNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Usman Khalid Robert H. Jenkins Robert Andrews Gilda Pino-Chavez Benjamin C. Cossins Rafael Chavez Timothy Bowen Donald J. Fraser Determination of a microRNA signature of protective kidney ischemic preconditioning originating from proximal tubules
description	Abstract Ischemic preconditioning (IPC) is effective in limiting subsequent ischemic acute kidney injury in experimental models. MicroRNAs are an important class of post-transcriptional regulator and show promise as biomarkers of kidney injury. We evaluated the time- and dose-dependence of benefit from IPC in a rat model of functional (bilateral) ischemia–reperfusion injury (IRI). We found optimal protection from subsequent injury following short, repetitive sequences of preconditioning insult. We subsequently used hybridization array and microRNA sequencing to characterize microRNA signatures of protective IPC and of IRI. These approaches identified a profile of microRNA changes consequent on IRI, that were limited by prior IPC. To localize these signals within the kidney, we used laser capture microdissection and RT-qPCR to measure microRNA abundance in nephron segments, pinpointing microRNA changes principally to glomeruli and proximal tubules. Our data describe a unique microRNA signature for IRI in the rat kidney. Pulsatile IPC reduces kidney damage following IRI and diminishes this microRNA signal. We have also identified candidate microRNAs that may act as biomarkers of injury and therapeutic targets in this context.
format	article
author	Usman Khalid Robert H. Jenkins Robert Andrews Gilda Pino-Chavez Benjamin C. Cossins Rafael Chavez Timothy Bowen Donald J. Fraser
author_facet	Usman Khalid Robert H. Jenkins Robert Andrews Gilda Pino-Chavez Benjamin C. Cossins Rafael Chavez Timothy Bowen Donald J. Fraser
author_sort	Usman Khalid
title	Determination of a microRNA signature of protective kidney ischemic preconditioning originating from proximal tubules
title_short	Determination of a microRNA signature of protective kidney ischemic preconditioning originating from proximal tubules
title_full	Determination of a microRNA signature of protective kidney ischemic preconditioning originating from proximal tubules
title_fullStr	Determination of a microRNA signature of protective kidney ischemic preconditioning originating from proximal tubules
title_full_unstemmed	Determination of a microRNA signature of protective kidney ischemic preconditioning originating from proximal tubules
title_sort	determination of a microrna signature of protective kidney ischemic preconditioning originating from proximal tubules
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f300b59f825445b7aca92d3fdb870348
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Determination of a microRNA signature of protective kidney ischemic preconditioning originating from proximal tubules

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