Abstract
Glomerular visceral epithelial cells, also known as podocytes, are highly specialized epithelial cells that cover the outer aspect of the glomerular basement membrane (GBM). Podocytes consist of cell bodies, major processes and foot processes of neighbouring cells, with filtration slits being bridged by the slit membrane between these filtration slits. The function of podocytes is largely based on their specialized cell architecture ; functions include stabilization of glomerular capillaries and participation in the barrier function of glomerular filter. Podocytes therefore form the final barrier to protein loss, which explains why podocyte injury is typically associated with marked proteinuria. Chronic podocyte injury may lead to podocyte detachment from GBM. Podocyte injury is involved in many forms of human and experimental glomerular disease. Based on recent insights into the molecular pathology of podocyte injury, at least four major causes have been identified that lead to the uniform reaction of FP (foot process) effacement and proteinuria (1) interference with the SD (slit diaphragm) complex and its lipid rafts ; (2) direct interference with the actin cytoskeleton; (3) interference with the GBM or with podocyte GBM interaction; and (4) inteference with the negative charge of podocytes. Ongoing studies in many laboratories are investigating the dynamic relationship between SD proteins, the actin cytoskeleton, and the dynamics of FP structure in nephrotic syndrome and focal segmental glomerulosclerosis. Such studies will potentially translate into more refined treatment strategies and the prevention of proteinuria and progressive glomerular disease.
