Your browser doesn't support javascript.
loading
The AGE receptor, OST48 drives podocyte foot process effacement and basement membrane expansion (alters structural composition).
Zhuang, Aowen; Yap, Felicia Y T; Borg, Danielle J; McCarthy, Domenica; Fotheringham, Amelia; Leung, Sherman; Penfold, Sally A; Sourris, Karly C; Coughlan, Melinda T; Schulz, Benjamin L; Forbes, Josephine M.
  • Zhuang A; Glycation and Diabetes Complications Mater Research Institute - The University of Queensland Translational Research Institute Woolloongabba Qld Australia.
  • Yap FYT; Faculty of Medicine University of Queensland St Lucia Qld Australia.
  • Borg DJ; Baker Heart and Diabetes Institute Melbourne Vic Australia.
  • McCarthy D; Baker Heart and Diabetes Institute Melbourne Vic Australia.
  • Fotheringham A; Glycation and Diabetes Complications Mater Research Institute - The University of Queensland Translational Research Institute Woolloongabba Qld Australia.
  • Leung S; Glycation and Diabetes Complications Mater Research Institute - The University of Queensland Translational Research Institute Woolloongabba Qld Australia.
  • Penfold SA; Glycation and Diabetes Complications Mater Research Institute - The University of Queensland Translational Research Institute Woolloongabba Qld Australia.
  • Sourris KC; Glycation and Diabetes Complications Mater Research Institute - The University of Queensland Translational Research Institute Woolloongabba Qld Australia.
  • Coughlan MT; Baker Heart and Diabetes Institute Melbourne Vic Australia.
  • Schulz BL; Baker Heart and Diabetes Institute Melbourne Vic Australia.
  • Forbes JM; Department of Diabetes Central Clinical School Monash University Melbourne Vic Australia.
Endocrinol Diabetes Metab ; 4(3): e00278, 2021 Jul.
Article en En | MEDLINE | ID: mdl-34277994
ABSTRACT

AIMS:

The accumulation of advanced glycation end products is implicated in the development and progression of diabetic kidney disease. No study has examined whether stimulating advanced glycation clearance via receptor manipulation is reno-protective in diabetes. Podocytes, which are early contributors to diabetic kidney disease and could be a target for reno-protection. MATERIALS AND

METHODS:

To examine the effects of increased podocyte oligosaccharyltransferase-48 on kidney function, glomerular sclerosis, tubulointerstitial fibrosis and proteome (PXD011434), we generated a mouse with increased oligosaccharyltransferase-48kDa subunit abundance in podocytes driven by the podocin promoter.

RESULTS:

Despite increased urinary clearance of advanced glycation end products, we observed a decline in renal function, significant glomerular damage including glomerulosclerosis, collagen IV deposition, glomerular basement membrane thickening and foot process effacement and tubulointerstitial fibrosis. Analysis of isolated glomeruli identified enrichment in proteins associated with collagen deposition, endoplasmic reticulum stress and oxidative stress. Ultra-resolution microscopy of podocytes revealed denudation of foot processes where there was co-localization of oligosaccharyltransferase-48kDa subunit and advanced glycation end-products.

CONCLUSIONS:

These studies indicate that increased podocyte expression of oligosaccharyltransferase-48 kDa subunit results in glomerular endoplasmic reticulum stress and a decline in kidney function.
Asunto(s)
Palabras clave

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Nefropatías Diabéticas / Podocitos Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Año: 2021 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Nefropatías Diabéticas / Podocitos Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Año: 2021 Tipo del documento: Article