Modulation of the cellular expression of circulating advanced glycation end-product receptors in type 2 diabetic nephropathy

Research output: Contribution to journalJournal articleResearchpeer-review

Karly C Sourris, Brooke E Harcourt, Sally A Penfold, Felicia Y T Yap, Amy L Morley, Philip E Morgan, Michael Jonathan Davies, Scott T Baker, George Jerums, Josephine M Forbes

BACKGROUND: Advanced glycation end-products (AGEs) and their receptors are prominent contributors to diabetic kidney disease.

METHODS: Flow cytometry was used to measure the predictive capacity for kidney impairment of the AGE receptors RAGE, AGE-R1, and AGE-R3 on peripheral blood mononuclear cells (PBMCs) in experimental models of type 2 diabetes (T2DM) fed varied AGE containing diets and in obese type 2 diabetic and control human subjects.

RESULTS: Diets high in AGE content fed to diabetic mice decreased cell surface RAGE on PBMCs and in type 2 diabetic patients with renal impairment (RI). All diabetic mice had elevated Albumin excretion rates (AERs), and high AGE fed dbdb mice had declining Glomerular filtration rate (GFR). Cell surface AGE-R1 expression was also decreased by high AGE diets and with diabetes in dbdb mice and in humans with RI. PBMC expression of AGE R3 was decreased in diabetic dbdb mice or with a low AGE diet.

CONCLUSIONS: The most predictive PBMC profile for renal disease associated with T2DM was an increase in the cell surface expression of AGE-R1, in the context of a decrease in membranous RAGE expression in humans, which warrants further investigation as a biomarker for progressive DN in larger patient cohorts.

Original languageEnglish
JournalJournal of Diabetes Research
Volume2010
Pages (from-to)974681
ISSN2314-6745
DOIs
Publication statusPublished - 2010
Externally publishedYes

    Research areas

  • Animals, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Flow Cytometry, Glycosylation End Products, Advanced, Male, Mice, Mice, Inbred C57BL, Receptors, Immunologic

ID: 129669850