Abstract
Our studies have shown the cytoplasmic domain of the receptor for advanced glycation endproducts (RAGE) binds to the formin molecule, diaphanous-1 (mDia1). mDia1 is a member of the formin family of intracellular molecules involved in cellular migration which act as effectors of Rho GTPase signaling. In RAGE-expressing cells devoid of mDia1, incubation with RAGE ligands failed to generate reactive oxygen species or activate key signaling cellular stress pathways. Our preliminary data reveal that mDia1 expression is increased in human and murine diabetic kidneys and expression patterns of mDia1 are highly analogous to RAGE expression patterns. In the diabetic glomerulus, RAGE and mDia1 are highly expressed in podocytes. While the role of RAGE has been shown to play a key role in the development of DN, the potential contribution of mDia1 has yet to be elucidated. Therefore, we tested the hypothesis that mDia1 contributes to the development of diabetic renal disease in a murine model. This preliminary study suggests that deletion of mDia1 in mice results in a substantial protection against indices of renal disease by reducing podocyte effacement, inflammation and fibrosis in type 1 DM.
Published Version
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