Dataset: Differential Expression of Ove26(Diabetic) vs FVB(Nondiabetic) mice

Objective – Previous studies showed that genetic deletion or pharmacological blockade of the Receptor for Advanced Glycation Endproducts (RAGE) prevents the early structural changes in the glomerulus associated with diabetic nephropathy (DN). To overcome limitations of mouse models that lack the progressive glomerulosclerosis observed in humans, we studied the contribution of RAGE to DN in the OVE26 type 1 mouse, a model of progressive glomerulosclerosis and decline of renal function. Research Design and Methods – We bred OVE26 mice with homozygous RAGE knock out (RKO) mice and examined structural changes associated with DN and used inulin clearance studies and albumin:creatinine measurements to assess renal function. Affymetrix Mouse 430.2 microarrays were used to measure the differential expression of OVE26vsFVB(WT) mice. Transcriptional changes in the TGF-β1 and Plasminogen activator inhibitor 1 gene products were measured by pcr to investigate mechanisms underlying accumulation of mesangial matrix in OVE26 mice. Results - Deletion of RAGE in OVE26 mice reduced nephromegaly, mesangial sclerosis, cast formation, glomerular basement membrane thickening, podocyte effacement, and albuminuria. The significant 29% reduction in glomerular filtration rate observed in OVE26 mice was completely prevented by deletion of RAGE. Increased transcription of the genes for Plasminogen activator inhibitor 1, TGF-β1, TGF-β induced, α1- (IV) collagen observed in OVE26 renal cortex significantly reduced in OVE26 RKO kidney cortex. ROCK1 activity was significantly lower in OVE26 RKO compared to OVE26 kidney cortex. Conclusions - These data provide compelling evidence for critical roles for RAGE in the pathogenesis of DN and suggest that strategies targeting RAGE in long-term diabetes may prevent loss of renal function. The differential gene expression of OVE26 (diabetics) vs FVB (nodiabetic WT) mice was measured using Affymetrix Mouse 430.2 arrays.

Species:

mouse

Samples:

7

Source:

E-GEOD-20844

PubMed:

20627935

Updated:

Dec.12, 2014

Registered:

Nov.11, 2014