The Receptor for Advanced Glycation Endproducts (RAGE) is a multiligand receptor of the immunoglobulin superfamily that is upregulated in diabetic tissues includeing the vasculature and glomerular epithelial cells. Previous studies have identified that the ligands of RAGE, such as AGEs and S1007calgranulins, are expressed to increased degrees in diabetic tissues. Previous studies have demonstrated that pharmacologic blockade of RAGE, using soluble RAGE, RAGE null mice or signal transduction deficient mutants, protects against several complications of diabetes, including in the vasculature the kidney. The purpose of this application is to explore in depth for the first time the implications of RAGE deletion in db/db mice. Db/db mice are a murine model of type 2, insulin-resistant diabetes. We hypothesize that the adverse impact of RAGE/ligand signaling will be attenuated in db/db mice that lack RAGE. We will perform a thorough time course to assess the impact of RAGE on the pathogenesis of diabetic nephropathy and diabetic vascular perturbations. In this application, we will dissect the impact of the RAGE/ligand interactions and the resulting signaling pathways using RAGE-expressing db/db mice and db/db mice genetically devoid of RAGE. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK076345-03
Application #
7463839
Study Section
Special Emphasis Panel (ZRG1-F06-J (20))
Program Officer
Rankin, Tracy L
Project Start
2006-08-01
Project End
2009-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
3
Fiscal Year
2008
Total Cost
$48,796
Indirect Cost
Name
Columbia University (N.Y.)
Department
Surgery
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
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Varney, Michael D; Valdes, Ana Maria; Carlson, Joyce A et al. (2010) HLA DPA1, DPB1 alleles and haplotypes contribute to the risk associated with type 1 diabetes: analysis of the type 1 diabetes genetics consortium families. Diabetes 59:2055-62
Guo, Jiancheng; Ananthakrishnan, Radha; Qu, Wu et al. (2008) RAGE mediates podocyte injury in adriamycin-induced glomerulosclerosis. J Am Soc Nephrol 19:961-72