Abstract | AIMS: 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.
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Authors | Aowen Zhuang, Felicia Y T Yap, Danielle J Borg, Domenica McCarthy, Amelia Fotheringham, Sherman Leung, Sally A Penfold, Karly C Sourris, Melinda T Coughlan, Benjamin L Schulz, Josephine M Forbes |
Journal | Endocrinology, diabetes & metabolism
(Endocrinol Diabetes Metab)
Vol. 4
Issue 3
Pg. e00278
(Jul 2021)
ISSN: 2398-9238 [Electronic] England |
PMID | 34277994
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2021 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. |
Chemical References |
- Glycation End Products, Advanced
- Receptor for Advanced Glycation End Products
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Topics |
- Animals
- Diabetic Nephropathies
(etiology, metabolism)
- Glomerular Basement Membrane
(metabolism)
- Glycation End Products, Advanced
(metabolism)
- Mice
- Podocytes
(metabolism)
- Receptor for Advanced Glycation End Products
(metabolism)
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