Podocytes (also known as visceral epithelial cells) are highly specialized cells found in the glomeruli of kidney nephrons. Podocytes wrap the external surface of the basal lamina of the glomerular capillaries (Figure 1). The morphology of podocytes is very complex and their main role is to filtrate the blood plasma, which happens in the kidney glomeruli.
Podocytes are really morphologically complex cells (Figure 2). They are polarized cells, with an apical domain toward the Bowman's capsule and the other toward the basal lamina of the capillary endothelium. Podocytes show a flat cytoplasm with a visible rise containing the nucleus. They have a well-developed Golgi apparatus, abundant endoplasmic reticulum, and many mitochondria and lysosomes. The cytoplasm sends many tiny finger-like protrusions that wrap the basal lamina of capillaries. These protrusions are called intergidital processes because protrusions coming from adjoining podocytes may be intermingled. The organelles are scarce in the interdigital processes. The form and length of these little expansions depend on the actin filaments. Neighbor interdigital processes are connected by molecular complexes known as slit diaphragms, and they show a dense glycocalix with a negative net charge, which make interdigital processes not to touch one another. Thus, their distribution on the surface of capillaries is rather homogeneous. Diaphragm slits are about 30 a 40 nm in length, looking like adherent junctions (with a dense region). They contains cadherins ZO-1 protein, nephrin, FAT an NEPH-1 proteins.
Podocytes are attached to the basal lamina by alpha3-beta1 integrins and by distroglycans. Both are connected to actin filament in the cytoplasm. Cytoskeleton is also responsible for the connection between interdigital processes through the slit diaphragm.
Podocytes are generated during the kidney formation by differentiation from messenchymal cells. These messenchymal cells also give the Bowman's capsule and the rest of the cells of the glomerulus, including endothelial and mesangial cells. Initially, podocytes are polygonal cells connected by gap junctions. However, when capillaries are developing, podocytes change the morphology to wrap those capillaries, lose gap-junctions and express specific molecules like synaptopodin, as well as the intermediate filament vimentin. The WT-1 protein is characteristic of podocytes both during development and at adult functional stage.
Unlike the mesangial cells of the glomerulus, the division rate of podocytes is very low. It makes sense since podocyte divisions may disturb the glomerulus organization and therefore the filtering capacity. Most podocytes are in a quiescent state maintained by a constant synthesis of mitotic inhibitors. Podocytes are not able to replace other died podocytes or cover enlargements of the capillary basal lamina with new cells. Experimentally, podocytes can be induced to proliferate. However, only the nucleus is divided and there is no cytokinesis. The decrease in the number of podocytes in a glomerulus is compensated by increasing the cell expansions of the already present podocytes.
Podocytes are involved in the filtration that takes place in the glomerulus. They are also important for preserving the structure of the glomerulus. Together with the endothelium and the basal lamina, podocytes are the third component of the filtration barrier. This barrier selects molecules according to their size and electrical charge, so that large molecules and ions are not allowed to cross. The less selective part of the barrier is the diaphragm slit between the interdigital processes.
Podocytes contribute to the basal lamina by synthesizing and releasing components part of its components. Basal lamina contains type IV collagen, laminin, entactin, agrin and perlecan. It is in permanent renewing and this is essential for filtering. Therefore, podocytes are also responsible for the filtration capability of the basal lamina. Furthermore, failures in interdigital processes led to filtering flaws and some pathologies like proteinuria.
The mechanical resistance of podocytes counterstans the hydraulic pressure of blood in capillaries, avoiding the breakage or distortion of the blood vessels. The mechanical strength is provided by the interdigital processes, which contain a cytoskeleton made up of mainly actin filament that is connected to the basal lamina through integrins. The ability of actin/myosin for producing contractions make adjustable the intensity and pressure of the wrapping around the capillaries, which also influence the filtration capacity.
Pavenstädt H, Kriz W, Kretzler M. 2003. Cell biology of the glomerular podocyte. Physiologycal reviews 83: 253-307.