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Imaging of Podocytic Proteins Nephrin, Actin, and Podocin with Expansion Microscopy
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The AGE receptor, OST48 drives podocyte foot process effacement and basement membrane expansion (alters structural

Aowen Zhuang1,2,3, Felicia Y T Yap3, Danielle J Borg1

  • 1Glycation and Diabetes Complications Mater Research Institute - The University of Queensland Translational Research Institute Woolloongabba Qld Australia.

Endocrinology, Diabetes & Metabolism
|July 19, 2021
PubMed
Abstract

Insights

Increased podocyte oligosaccharyltransferase-48kDa subunit expression worsened diabetic kidney disease, causing renal decline and glomerular damage despite enhanced advanced glycation end-product clearance.

Area of Science:

  • Nephrology
  • Diabetology
  • Molecular Biology

Background:

  • Diabetic kidney disease (DKD) is linked to advanced glycation end-product (AGE) accumulation.
  • Podocytes are crucial in DKD pathogenesis and potential targets for renoprotection.
  • The role of AGE clearance via receptor manipulation in DKD remains unexplored.

Purpose of the Study:

  • To investigate the impact of enhanced podocyte oligosaccharyltransferase-48kDa subunit (OST48) on kidney function in diabetes.
  • To determine if increased OST48 in podocytes affects glomerular sclerosis, tubulointerstitial fibrosis, and kidney proteome.

Main Methods:

  • Generated a transgenic mouse model with podocyte-specific overexpression of OST48 driven by the podocin promoter.
  • Assessed kidney function, glomerular damage (glomerulosclerosis), tubulointerstitial fibrosis, and urinary AGE clearance.
  • Performed proteomic analysis of isolated glomeruli and ultra-resolution microscopy of podocytes.

Main Results:

  • Despite increased urinary AGE clearance, mice exhibited impaired renal function and significant glomerular damage.
  • Observed glomerulosclerosis, collagen IV deposition, GBM thickening, podocyte foot process effacement, and tubulointerstitial fibrosis.
  • Glomeruli showed enrichment in proteins related to collagen deposition, ER stress, and oxidative stress; OST48 co-localized with AGEs in podocyte foot processes.

Conclusions:

  • Increased podocyte OST48 expression exacerbates DKD.
  • This overexpression leads to glomerular ER stress and a decline in kidney function.
  • Targeting OST48 may not be a viable renoprotective strategy in diabetic nephropathy.
Keywords:
advanced glycation end‐product receptor 1advanced glycation end‐productsdiabetesdiabetic kidney diseaseendoplasmic reticulum stressoligosaccharyltransferase‐48 diabetic nephropathy

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