Grant: Operating Grant

The glomerulus is the filtration unit of the kidney. It filters water and small molecules including body wastes while retaining large molecules essential for body function. When this barrier function is impaired, proteinuria occurs, which is often followed by kidney failure. Visceral glomerular epithelial cells (commonly known as 'podocytes') are critical for structural integrity as well as barrier function of the glomerulus. Recent researches highlighted the importance of the structural proteins (actin cytoskeleton) in podocytes for their function. The proposed research will define how podocytes maintain the structural and functional integrity and how podocyte injury leads to proteinuria. We hypothesize that various small Rho-GTPases act together to modulate the actin cytoskeleton and maintain podocyte morphology and function and that when the balance of various signaling pathways is disturbed, it leads to proteinuria. Cultured cells as well as experimental models will be used to address this hypothesis. The result of the research is likely to give insights into the pathogenesis of various proteinuric glomerular diseases such as membranous nephropathy, minimal change disease, and diabetic nephropathy, and contribute to the development of the better therapeutic approach to glomerular disease.