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Podocytes are cells in Bowman's capsule in the that wrap around capillary of the glomerulus. Podocytes make up the epithelial lining of Bowman's capsule, the third layer through which filtration of blood takes place. Bowman's capsule filters the blood, retaining large such as while smaller molecules such as water, salts, and are filtered as the first step in the formation of urine. Although various viscera have epithelium layers, the name visceral epithelial cells usually refers specifically to podocytes, which are specialized epithelial cells that reside in the visceral layer of the capsule.
The podocytes have long primary processes called ''trabeculae'' that form secondary processes known as ''pedicels'' or foot processes (for which the cells are named ''[[wikt:podo-#Prefix|podo-]]'' + ''[[wikt:-cyte#Suffix|-cyte]]''). The pedicels wrap around the capillaries and leave slits between them. Blood is filtered through these slits, each known as a '''filtration slit''', '''slit diaphragm''', or '''slit pore'''.(2025). 9781461437840, Springer Science+Business Media. ISBN 9781461437840Several proteins are required for the pedicels to wrap around the capillaries and function. When infants are born with certain defects in these proteins, such as [[nephrin]] and CD2AP, their kidneys cannot function. People have variations in these proteins, and some variations may predispose them to [[kidney failure]] later in life. [[Nephrin]] is a [[zipper-like protein|Leucine zipper]] that forms the slit diaphragm, with spaces between the teeth of the zipper big enough to allow sugar and water through but too small to allow proteins through. Nephrin defects are responsible for congenital kidney failure. CD2AP regulates the podocyte cytoskeleton and stabilizes the slit diaphragm.
There are numerous coated vesicles and coated pits along the basolateral domain of the podocytes which indicate a high rate of vesicular traffic.
Podocytes possess a well-developed endoplasmic reticulum and a large Golgi apparatus, indicative of a high capacity for protein synthesis and post-translational modifications.
There is also growing evidence of a large number of multivesicular bodies and other lysosome components seen in these cells, indicating a high endocytosis activity.
Dynamic changes in glomerular capillary pressure exert both tensile and stretching forces on podocyte foot processes, and can lead to mechanical strain on their cytoskeleton. Concurrently, fluid flow shear stress is generated by the movement of glomerular ultrafiltrate, exerting a tangential force on the surface of these foot processes.
In order to preserve their intricate foot process architecture, podocytes require a substantial ATP expenditure to maintain their structure and cytoskeletal organization, counteract the elevated glomerular capillary pressure and stabilize the capillary wall.
Podocytes are also involved in regulation of glomerular filtration rate (GFR). When podocytes contract, they cause closure of filtration slits. This decreases the GFR by reducing the surface area available for filtration.
Disruption of the filtration slits or destruction of the podocytes can lead to massive proteinuria, where large amounts of protein are lost from the blood.
An example of this occurs in the congenital disorder Finnish-type nephrosis, which is characterised by neonatal proteinuria leading to end-stage kidney failure. This disease has been found to be caused by a mutation in the nephrin gene.
In 2002 Professor Moin Saleem at the University of Bristol made the first conditionally immortalised human podocyte cell line. This meant that podocytes could be grown and studied in the lab. Since then many discoveries have been made. Nephrotic syndrome occurs when there is a breakdown of the glomerular filtration barrier. The podocytes form one layer of the filtration barrier. Genetic mutations can cause podocyte dysfunction leading to an inability of the filtration barrier to restrict urinary protein loss. There are currently 53 genes known to play a role in genetic nephrotic syndrome. In idiopathic nephrotic syndrome, there is no known genetic mutation. It is thought to be caused by a hitherto unknown circulating permeability factor. Recent evidence suggests that the factor could be released by T-cells or B-cells, podocyte cell lines can be treated with plasma from patients with nephrotic syndrome to understand the specific responses of the podocyte to the circulating factor. There is growing evidence that the circulating factor could be signalling to the podocyte via the PAR-1 receptor.
Presence of podocytes in urine has been proposed as an early diagnostic marker for preeclampsia.
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