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dc.contributor.authorSmith, Stephanie F
dc.contributor.authorHosgood, Sarah
dc.contributor.authorNicholson, Michael
dc.date.accessioned2019-04-05T23:32:25Z
dc.date.available2019-04-05T23:32:25Z
dc.date.issued2019-01
dc.identifier.issn0085-2538
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/291268
dc.description.abstractRenal ischemia-reperfusion injury (IRI) is a significant clinical challenge faced by clinicians perioperatively in kidney transplantation. Recent work has demonstrated the key importance of transmembrane receptors in the injured tubular epithelial cell, most notably Toll-like receptors, activated by exogenous and endogenous ligands in response to external and internal stresses. Through sequential protein-protein interactions, the signal is relayed deep into the core physiological machinery of the cell, having numerous effects from upregulation of pro-inflammatory gene products through to modulating mitochondrial respiration. Inter-pathway cross talk facilitates a co-ordinated response at an individual cellular level, as well as modulating the surrounding tissue's microenvironment through close interactions with the endothelium and circulating leukocytes. Defining the underlying cellular cascades involved in IRI will assist the identification of novel interventional targets to attenuate IRI with the potential to improve transplantation outcomes. We present a focused review of 3 key cellular signalling pathways in the injured tubular epithelial cell that have been the focus of much research over the past 2 decades: toll-like receptors, sphingosine-1-phosphate receptors and hypoxia inducible factors. We provide a unique perspective on the potential clinical translations of this recent work in the transplant setting. This is particularly timely with the recent completion of phase I and ongoing phase 2 clinical trials of inhibitors targeting specific components of these signaling cascades.
dc.format.mediumPrint
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectKidney Tubules
dc.subjectEpithelial Cells
dc.subjectHumans
dc.subjectKidney Failure, Chronic
dc.subjectReperfusion Injury
dc.subjectReceptors, Lysosphingolipid
dc.subjectKidney Transplantation
dc.subjectSignal Transduction
dc.subjectToll-Like Receptors
dc.subjectBasic Helix-Loop-Helix Transcription Factors
dc.subjectHypoxia-Inducible Factor 1
dc.subjectClinical Trials, Phase II as Topic
dc.subjectAllografts
dc.titleIschemia-reperfusion injury in renal transplantation: 3 key signaling pathways in tubular epithelial cells.
dc.typeArticle
prism.endingPage56
prism.issueIdentifier1
prism.publicationDate2019
prism.publicationNameKidney Int
prism.startingPage50
prism.volume95
dc.identifier.doi10.17863/CAM.38447
dcterms.dateAccepted2018-10-02
rioxxterms.versionofrecord10.1016/j.kint.2018.10.009
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-01
dc.contributor.orcidHosgood, Sarah [0000-0002-8039-143X]
dc.contributor.orcidNicholson, Michael [0000-0001-7620-0664]
dc.identifier.eissn1523-1755
rioxxterms.typeJournal Article/Review


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International