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Investigator Highlights

Dr. Marc Tatar

Marc Tatar is Professor in The Division of Biology and Medicine at Brown University. Current work in the Tatar laboratory focuses on genetic analysis of Drosophila to understand how insulin/IGF signals and lipid hormones regulate disease processes.

Chronic aldosterone induction of renal fibrosis in Drosophila

Chronic elevated aldosterone is a feature of diabetes that contributes to complications including heart failure and progressive renal disease marked by inflammation, proteinuria, and fibrosis. Aldosterone is an essential component of the renin-angiotensin system normally tasked to modulate blood pressure and fluid balance. In the short term aldosterone may also foster repair of damaged renal tissue, yet excessive, prolonged production appears to promote kidney failure. How aldosterone actually triggers disease responses is unknown and may involve ‘non-genomic signaling’ independent of its canonical nuclear hormone, mineralocorticoid receptor. We have found a GPCR in Drosophila through which aldosterone induces renal fibrosis in the fly. Chronic administration of aldosterone to adult Drosophila leads to the accumulation of collagen IV-like pericardin in the extracellular matrix of the fly kidney, and produces proteinuria and intolerance to high salt diet. Induction of collagen/pericardin requires the dual agonist GPRC dopEcR, homolog of mammalian GPER1 (GPR30). This pilot application will develop our findings into a working Drosophila model of diabetes associated hyper-aldosteronism by characterizing Malpighian tubule and nephrocyte specific dysfunction induced by the human steroid, and by showing this nephropathy results from accumulated collagen/pericardin under the control of GPCR dopEcR.