Podocyte

Diagram showing the basic physiologic mechanisms of the kidney

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]

Podocytes secrete and maintain the basement membrane.[2]

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 lysosomal components seen in these cells, indicating a high endocytic activity.

Scheme of filtration barrier (blood-urine) in the kidney.
A. The endothelial cells of the glomerulus; 1. pore (fenestra).
B. Glomerular basement membrane: 1. lamina rara interna 2. lamina densa 3. lamina rara externa
C. Podocytes: 1. enzymatic and structural protein 2. filtration slit 3. diaphragma

Pedicels of podocytes interdigitating to create numerous filtration slits around glomerular capillaries in 5000x electron micrograph

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]

Small molecules such as water, glucose, and ionic salts are able to pass through the filtration slits and form an ultrafiltrate in the tubular fluid, which is further processed by the nephron to produce urine.

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.

Morphologic patterns of podocyte injury.[12]

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] This meant that podocytes could be grown and studied in the lab. Since then many discoveries have been made. Nephrotis 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]

Presence of podocytes in urine has been proposed as an early diagnostic marker for preeclampsia.[20]

• List of human cell types derived from the germ layers
• List of distinct cell types in the adult human body

• Anatomy photo: Urinary/mammal/vasc1/vasc1 - Comparative Organology at University of California, Davis - "Mammal, renal vasculature (EM, High)
• Histology image: 22401loa – Histology Learning System at Boston University - ". Ultrastructure of the Cell: podocytes and glomerular capillaries"
• UIUC Histology Subject 1400
• podocyte.ca at Samuel Lunenfeld Research Institute
• Histology image: 22402loa – Histology Learning System at Boston University
• Histology image: 22403loa – Histology Learning System at Boston University