Podocyte and Parietal Epithelial Cell Interactions in Health and Disease

Abstract

The glomerulus has 3 resident cells namely mesangial cells that produce the mesangial matrix, endothelial cells that line the glomerular capillaries, and podocytes that cover the outer surface of the glomerular basement membrane. Parietal epithelial cells (PrECs), which line the Bowman's capsule are not part of the glomerular tuft but may have an important role in the normal function of the glomerulus. A significant progress has been made in recent years regarding our understanding of the role and function of these cells in normal kidney and in kidneys with various types of glomerulopathy. In crescentic glomerulonephritis necrotizing injury of the glomerular tuft results in activation and leakage of fibrinogen which provides the trigger for excessive proliferation of PrECs giving rise to glomerular crescents. In cases of collapsing glomerulopathy, podocyte injury causes collapse of the glomerular capillaries and activation and proliferation of PrECs, which accumulate within the urinary space in the form of pseudocrescents. Many of the noninflammatory glomerular lesions such as focal segmental glomerulosclerosis and global glomerulosclerosis also result from podocyte injury which causes variable loss of podocytes. In these cases podocyte injury leads to activation of PrECs that extend on to the glomerular tuft where they cause segmental and/or global sclerosis by producing excess matrix, resulting in obliteration of the capillary lumina. In diabetic nephropathy, in addition to increased matrix production in the mesangium and glomerular basement membranes, increased loss of podocytes is an important determinant of long-term prognosis. Contrary to prior belief there is no convincing evidence for an active podocyte proliferation in any of the above mentioned glomerulopathies.