PODOCYTES: CHARACTERISTICS, HISTOLOGY AND FUNCTIONS - BIOLOGY - 2025

The podocytes are one of four types of cells found in the renal glomeruli. Its name is due to the elaborate processes or pedicels characteristic of its structure (foot pruning, and cell cyto).

It is necessary to have a well-defined structure and function of the kidneys to understand the characteristics and functions of podocytes. The kidneys are organs specialized in the filtration of blood and the formation of urine. These are made up of nephrons, which are the basic units through which urine is produced.

Graphic representation of podocytes (Source: OpenStax College via Wikimedia Commons)

A nephron is made up, functionally speaking, of: 1) a filtration unit known as the renal corpuscle or glomerulus (which comes from the Latin word glomus, which means a ball of wool) and 2) a segmented tubular reabsorption compartment.

Four different types of cells are found in the glomerulus:

- Glomerular endothelial cells.

- The podocitos.

- Mesangial cells.

- The parietal epithelial cells.

From an architectural point of view, a glomerulus is composed of a glomerular “plume” and Bowman's capsule. The basic unit of each glomerular plume is a capillary, which is founded on a basement membrane.

Podocytes, also known as perivascular cells, are "atypical" epithelial cells, characterized by having a cell body from which short feet and long processes or projections project.

Characteristics and histology of podocytes

These differentiated cells are found on the outer surface of the glomerular capillaries, that is, they belong to the glomerular tufts. Its main function, as well as that of many kidney cells, has to do with their participation in the filtration process.

During their normal development, podocytes arise from a cuboidal "progenitor" epithelial cell that extends long projections. These branch into other primary and secondary processes, adopting an octopus-like structure, with multiple “feet”.

The feet, the shortest cellular projections of a podocyte, interdigitate (intertwine) with the feet of neighboring podocytes before joining glomerular capillaries. Later, these adhere to the basement membrane of the glomerulus to exert their functions in the filtration barrier.

If the podocytes are damaged, they go through a process through which they lose their projections and become diffuse or amorphous. This has as a consequence that the interdigitations between adjacent podocytes disappear, reducing their functions in blood filtration.

Structure

Podocytes have quite a complex architecture. Its general structure consists of a cell body, "larger" processes or projections, and "feet" that surround the glomerular capillaries.

The largest processes are known as "primary and secondary projections" and are composed of microtubules and intermediate filaments. The smallest processes are known as "feet" and are projections of the cytoskeleton, rich in actin filaments.

The “feet” of podocytes have a negatively charged covering or glycocalyx that faces the urinary space, which contributes to the maintenance of the architecture of these cells, thanks to the repulsion of charges caused by physical separation.

The function of podocytes depends mainly on their architecture, especially on the orderly maintenance of the "bundles" of contractile actin filaments that form the feet.

Podocytes are polarized kidney cells. They have three structural domains that are physically and functionally linked to the cytoskeleton of the feet. These domains are known as the apical membrane domain, the interaction sites between the feet are known as slit diaphragms, and the domain is known as the basement membrane.

The basement membrane domain and the cleft diaphragm are in direct contact with the basement membrane of the glomerulus, while the apical membrane domain (most of the cell body) is "facing" Bowman's space.

Interaction between podocytes

As mentioned a moment ago, the feet and the cytoskeletal projections of adjacent podocytes interact with each other, forming a kind of network that lines the glomerular capillaries.

These slit diaphragm domains between the feet of the podocytes are porous and, for this reason, serve as exit ports for the first urinary filtration. These sites have also been recognized for their role in the selective retention of high molecular weight plasma components.

Features

Together with the fenestrated endothelium monolayers of the vascular space, podocytes form the glomerular filtration barrier. This barrier facilitates the filtering of cations, electrolytes and medium-sized molecules, but restricts the passage of anions and macromolecules.

Therefore, the physical integrity of both cells and their projections, as well as the binding and interaction sites between them, is of great importance for the establishment and maintenance of the glomerular filtration barrier.

In addition to their active participation in urine production, podocytes have important functions in promoting proliferation, survival, and development of endothelial cells, since they secrete various pro-angiogenic factors, essential for the normal development of the glomerular endothelium.

Podocytes, together with the endothelial cells of the glomeruli, contribute to the formation of the glomerular basement membrane, since it has been shown that some of the collagen IV networks present there are produced by these cells.

Podocytes also function in the endocytosis of macromolecules and proteins that cross the basement membrane, which prevents the “clogging” of the filtration barrier.

Related diseases

When wounds or genetic defects occur in podocytes, some pathological conditions occur in humans. One of them is known as albuminuria, characterized by the excretion of albumin in the urine (due to errors during filtration).

Furthermore, since podocytes have a limited capacity for division once they have differentiated, their loss is one of the characteristic events of progressive kidney diseases.

References

1. Asanuma, K., & Mundel, P. (2003). The role of podocytes in glomerular pathobiology. Clin. Exp. Nephrol., 7, 255–259.
2. Garg, P. (2018). Nephrology A Review of Podocyte Biology. American Journal of Nephrology, 47, 3–13.
3. Greka, A., & Mundel, P. (2012). Cell Biology and Pathology of Podocytes. Annu. Rev. Physiol., 74, 299–323.
4. Mundel, P., & Kriz, W. (1995). Structure and function of podocytes: an update. Anat. Embryol., 385–397.
5. Reiser, J., & Altintas, MM (2016). Podocytes. F1000 Research, 5, 1–19.
6. Scott, RP, & Quaggin, SE (2015). The cell biology of renal filtration. J. Cell. Biol., 209 (2), 199-210.
7. Shankland, SJ, Pippin, JW, Reiser, J., & Mundel, P. (2007). Podocytes in culture: past, present, and future. Kidney International, 72, 26–36.