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

TY - JOUR

T1 - Modulation of the cellular expression of circulating advanced glycation end-product receptors in type 2 diabetic nephropathy

AU - Sourris, Karly C

AU - Harcourt, Brooke E

AU - Penfold, Sally A

AU - Yap, Felicia Y T

AU - Morley, Amy L

AU - Morgan, Philip E

AU - Davies, Michael Jonathan

AU - Baker, Scott T

AU - Jerums, George

AU - Forbes, Josephine M

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - Animals

KW - Diabetes Mellitus, Type 2

KW - Diabetic Nephropathies

KW - Flow Cytometry

KW - Glycosylation End Products, Advanced

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Receptors, Immunologic

U2 - 10.1155/2010/974681

DO - 10.1155/2010/974681

M3 - Journal article

C2 - 21318189

SN - 2314-6745

VL - 2010

SP - 974681

JO - Journal of Diabetes Research

JF - Journal of Diabetes Research

ER -