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

Khalid, Usman, Jenkins, Robert H., Andrews, Robert, Pino-Chavez, Gilda, Cossins, Benjamin C., Chavez, Rafael, Bowen, Timothy and Fraser, Donald J. 2021. Determination of a microRNA signature of protective kidney ischemic preconditioning originating from proximal tubules. Scientific Reports 11 (1) , 9862. 10.1038/s41598-021-89195-3

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher: Nature Research
ISSN: 2045-2322
Date of First Compliant Deposit: 25 August 2021
Date of Acceptance: 17 March 2021
Last Modified: 26 Aug 2021 11:15
URI: http://orca.cardiff.ac.uk/id/eprint/143659

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