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dc.contributor.authorHaley, Kathryn
dc.contributor.authorElshani, Mustafa
dc.contributor.authorUm, In Hwa
dc.contributor.authorBell, Cameron
dc.contributor.authorCaie, Peter David
dc.contributor.authorHarrison, David James
dc.contributor.authorReynolds, Paul Andrew
dc.identifier.citationHaley , K , Elshani , M , Um , I H , Bell , C , Caie , P D , Harrison , D J & Reynolds , P A 2021 , ' YAP translocation precedes cytoskeletal rearrangement in podocyte stress response : a podometric investigation of diabetic nephropathy ' , Frontiers in Physiology , vol. 12 , 625762 .
dc.identifier.otherPURE: 274298662
dc.identifier.otherPURE UUID: f98dcd98-1335-4439-b62e-bec9f9e96f0d
dc.identifier.otherORCID: /0000-0001-8738-1245/work/97129695
dc.identifier.otherORCID: /0000-0001-9041-9988/work/97129830
dc.identifier.otherORCID: /0000-0002-0031-9850/work/97129928
dc.identifier.otherScopus: 85111611999
dc.identifier.otherWOS: 000679131200001
dc.descriptionKH was funded by a University of St Andrews 600th Anniversary Ph.D. scholarship. ME and DH were supported by NHS Lothian.en
dc.description.abstractPodocyte loss plays a pivotal role in the pathogenesis of glomerular disease. However, the mechanisms underlying podocyte damage and loss remain poorly understood. Although detachment of viable cells has been documented in experimental Diabetic Nephropathy, correlations between reduced podocyte density and disease severity have not yet been established. YAP, a mechanosensing protein, has recently been shown to correlate with glomerular disease progression, however, the underlying mechanism has yet to be fully elucidated. In this study, we sought to document podocyte density in Diabetic Nephropathy using an amended podometric methodology, and to investigate the interplay between YAP and cytoskeletal integrity during podocyte injury. Podocyte density was quantified using TLE4 and GLEPP1 multiplexed immunofluorescence. Fourteen Diabetic Nephropathy cases were analyzed for both podocyte density and cytoplasmic translocation of YAP via automated image analysis. We demonstrate a significant decrease in podocyte density in Grade III/IV cases (124.5 per 106 μm3) relative to Grade I/II cases (226 per 106 μm3) (Student’s t-test, p<0.001), and further show that YAP translocation precedes cytoskeletal rearrangement following injury. Based on these findings we hypothesize that a significant decrease in podocyte density in late grade Diabetic Nephropathy may be explained by early cytoplasmic translocation of YAP.
dc.relation.ispartofFrontiers in Physiologyen
dc.rightsCopyright © 2021 Haley, Elshani, Um, Bell, Caie, Harrison and Reynolds. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en
dc.subjectDiabetic nephropathyen
dc.subjectAutomated image analysisen
dc.subjectHippo signalingen
dc.subjectQH426 Geneticsen
dc.titleYAP translocation precedes cytoskeletal rearrangement in podocyte stress response : a podometric investigation of diabetic nephropathyen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.Sir James Mackenzie Institute for Early Diagnosisen
dc.contributor.institutionUniversity of St Andrews.Centre for Biophotonicsen
dc.contributor.institutionUniversity of St Andrews.Cellular Medicine Divisionen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.description.statusPeer revieweden

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