YAP translocation precedes cytoskeletal rearrangement in podocyte stress response: a podometric investigation of diabetic nephropathy

Kathryn Haley, Mustafa Elshani, In Hwa Um, Cameron Bell, Peter David Caie, David James Harrison, Paul Andrew Reynolds*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

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.
Original languageEnglish
Article number625762
Number of pages10
JournalFrontiers in Physiology
Volume12
DOIs
Publication statusPublished - 15 Jul 2021

Keywords

  • Podocytes
  • Diabetic nephropathy
  • Podometrics
  • YAP
  • Automated image analysis
  • Hippo signaling

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