Podocyte injury and targeting therapy: an update

Abstract

Podocyte injury is a central event in the development of glomerulosclerosis. This review highlights contributions from the past year to our understanding of mechanisms of podocyte injury and implications for potential treatment strategies of glomerular disease. Rearrangement of the actin cytoskeleton, the backbone linking the slit diaphragm, apical domain and sole plate, serves as a common denominator during foot process effacement. Reports on the role of synaptopodin and CDK5 on actin dynamics as well as cathepsin L and B7.1 in subsequent cell migration have expanded our understanding of the podocyte response to injury. Mounting evidence supports an expanding role of the slit diaphragm in signal transduction to mediate downstream cellular responses, including prosurvival effects of the integral proteins nephrin and CD2AP. The discovery that TRPC6 localizes to the slit diaphragm and identification of specific mutations of the transport channel in kindreds of familial focal segmental glomerulosclerosis implicate a causal role for aberrant calcium signaling in podocyte injury. Disruption of the dystroglycan complex, which anchors the podocyte to the underlying basement membrane, in states of foot process effacement may have implications for the recent finding of viable podocytes in the urine in glomerular disease. The resurgence of research in podocyte biology over the past decade underscores the importance of this unique cell in preserving glomerular structure and function. A greater understanding of the complex signaling mechanisms governing podocyte biology in health and disease will ultimately lead to novel therapeutic avenues for treating disorders of the podocyte.