RAGE/Diaph1, Diabetes, and Kidney Disease: Mechanisms and Novel Therapeutic Strategies
Technical Report,30 Sep 2018,29 Sep 2019
New York University School of Medicine New York United States
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In Year Two of the funded grant, we have substantial progress in the following critical areas First, we have established the breeding colonies for all four of the key mouse lines to test the roles of RAGE and DIAPH1 in podocytes and monocytesmacrophages in the pathogenesis of diabetes associated nephropathic changes in the kidney. As detailed in the full progress report, most of these animals males and females have already been rendered diabetic and are on time course. Many have already been sacrificed and the pathological analysis of tissues is underway. These samples are now with Dr. DAgati and the investigators are nave to the sample identification until the code is broken. Second, we have optimized podocyte isolation procedures as indicated in the grant application. This is a key step, which will enable us to probe mechanisms of RAGE and DIAPH1 biology in these cells. Third, Dr. Ramasamy identifies substantial progress in the development and validation of metabolomics and lipidomics assays here at NYU in order to understand detailed mechanisms of the role of these molecules in the diabetic kidney. Fourth, in the Aim 3 pharmacology study, our preliminary data on treated vs. untreated diabetic mice illustrates reduction in mesangial sclerosis, reduced thickening of the glomerular basement membrane and reduction in podocyte effacement in diabetic mice receiving RAGE229 medicated chow delivering 30mgkgday vs vehicle chow. Additional mice are on study and time course at this time to complete the indicated enrollment. Taken together, our work in Year 2 has been very productive and we await tissue and other analyses, as above, to render final conclusions.
- Medicine and Medical Research