Renal corpuscle structure
Blood flows in the afferent arteriole at the top, and out the efferent arteriole at the bottom. Blood flows through the capillaries of the glomerulus, where it is filtered by pressure. The podocytes (green) are wrapped around the capillaries. Blood is filtered through the slit diaphragm (or filtration slit), between the feet or processes of the podocytes. The filtered blood passes out the proximal tubule (yellow) on the right.
Podocytes are
cells in
Bowman's capsule in the
kidneys that wrap around
capillaries of the
glomerulus. Podocytes make up the epithelial lining of Bowman's capsule, the third layer through which
filtration of blood takes place.[1] Bowman's capsule filters the
blood, retaining large
molecules such as
proteins while smaller molecules such as
water,
salts, and
sugars are filtered as the first step in the formation of
urine. Although various
viscera have
epithelial 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
foot processes called pedicels, for which the cells are named (podo- + -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.[2] Several 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 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.[3][4]
Structure
Podocytes are found lining the Bowman's capsules in the nephrons of the kidney. The foot processes known as pedicels that extend from the podocytes wrap themselves around the
capillaries of the glomerulus to form the filtration slits. The pedicels increase the surface area of the cells enabling efficient
ultrafiltration.[5]
There is also growing evidence of a large number of multivesicular bodies and other
lysosomal components seen in these cells, indicating a high
endocytic activity.
Function
Podocytes have primary processes called trabeculae, which wrap around the
glomerular capillaries.[6] The trabeculae in turn have secondary processes called pedicels.[6] Pedicels interdigitate, thereby giving rise to thin gaps called filtration slits.[2] The slits are covered by slit diaphragms which are composed of a number of cell-surface proteins including
nephrin,
podocalyxin, and
P-cadherin, which restrict the passage of large
macromolecules such as
serum albumin and
gamma globulin and ensure that they remain in the bloodstream.[7] Proteins that are required for the correct function of the slit diaphragm include
nephrin,[8]NEPH1,
NEPH2,[9]podocin,
CD2AP.[10] and
FAT1.[11]
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.
Clinical significance
A loss of the foot processes of the podocytes (i.e., podocyte effacement) is a hallmark of
minimal change disease, which has therefore sometimes been called foot process disease.[13]
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.[14][further explanation needed] 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.[15] In idiopathic nephrotic syndrome, there is no known genetic mutation. It is thought to be caused by a hitherto unknown circulating permeability factor.[16] Recent evidence suggests that the factor could be released by T-cells or B-cells,[17][18] 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.[19][further explanation needed]
Presence of podocytes in urine has been proposed as an early diagnostic marker for
preeclampsia.[20]
^Neumann-Haefelin E, Kramer-Zucker A, Slanchev K, Hartleben B, Noutsou F, Martin K, et al. (June 2010). "A model organism approach: defining the role of Neph proteins as regulators of neuron and kidney morphogenesis". Human Molecular Genetics. 19 (12): 2347–2359.
doi:
10.1093/hmg/ddq108.
PMID20233749.