YAP translocation precedes cytoskeletal rearrangement in podocyte stress response : a podometric investigation of diabetic nephropathy
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Podocyte 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.
Haley , 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 . https://doi.org/10.3389/fphys.2021.625762
Frontiers in Physiology
Copyright © 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.
DescriptionKH was funded by a University of St Andrews 600th Anniversary Ph.D. scholarship. ME and DH were supported by NHS Lothian.
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