Cell Biology of the Podocyte

Background: The terminally differentiated and highly specialized glomerular epithelial cells called podocytes function as a major barrier to protein passaging from the intravascular glomerular capillaries to the extravascular urinary space. However, once injured in disease, increased passage of proteins leads to proteinuria, and a decrease in podocyte number underlies progressive glomerular scarring. Summary: Numerous proteins specific to podocytes enable their normal functions, including those that comprise the slit diaphragm to act as a size, charge and shape barrier, a rich actin cytoskeleton that enables mobility, and the production and secretion of growth factors required for normal glomerular endothelial cell health. When injured in podocyte diseases such as focal segmental glomerulosclerosis, minimal change disease, membranous nephropathy, diabetic kidney disease and others, several of these normal functions are disrupted, leading to changes in histological appearance, structure and function. These are typically manifest clinically by proteinuria and a decline in kidney function. Key Messages: Because of podocyte's inability to adequately proliferate, a decline in their number follows when cells undergo apoptosis, detachment, necrosis and altered autophagy in response to injury. This leads to progressive glomerular scarring. These mechanisms will be discussed in this chapter. Alterations in key slit diaphragm proteins lead to proteinuria, which will also be discussed. (C) 2014 S. Karger AG, Basel