Identification of the pathogenesis of nephrotic syndrome by analyses of signal transduction and proteome

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Slit diaphragm, an intercellular junction between renal glomerular epithelial cells (podocytes), is essential for the permselectivity in glomerular ultrafiltarion. To establish specific therapy for pediatric nephrotic syndrome, we focused on the structure and function of slit diaphragm (SD) and investigated the pathogenic mechanism of proteinuria and nephrotic syndrome. We revealed (I) the importance of dynamics of slit diaphragm turnover in the maintenance of slit diaphragm, (II) the novel component of slit diaphragm, (III) the mechanism of intracellular calcium concentration by slit diaphragm signaling, and (IV) the changes of expression of functional proteins in podocytes of nephrotic patients. Our data provide new molecular insights into the formation and maintenance of SD and its dysfunction in hereditary and idiopathic nephrotic syndrome.