Abstract
Podocytes, or glomerular epithelial cells, form the final layer in the glomerular capillary wall of the kidney. Along with the glomerular basement membrane and glomerular endothelial cells, they make up the glomerular filtration barrier which allows the passage of water and small molecules and, in healthy individuals, prevents the passage of albumin and other key proteins. The podocyte is a specialised and terminally differentiated cell with a specific cell morphology that is largely dependent on a highly dynamic underlying cytoskeletal network and that is essential for maintaining glomerular function and integrity in healthy kidneys. The RhoGTPases (RhoA, Rac1 and Cdc42), which act as molecular switches that regulate actin dynamics, are known to play a crucial role in maintaining the cytoskeletal and molecular integrity of the podocyte foot processes in a dynamic manner. Recently, novel protein interaction networks that regulate the RhoGTPases in the podocyte and that are altered by disease have been discovered. This review will discuss these networks and their potential as novel therapeutic targets in nephrotic syndrome. It will also discuss the evidence that they are direct targets for (a) steroids, the first-line agents for the treatment of nephrotic syndrome, and (b) certain kinase inhibitors used in cancer treatment, leading to nephrotoxicity.
Highlights
The kidney is vital for the maintenance of water and electrolyte homeostasis and for the removal of waste metabolites from the blood while retaining or reabsorbing useful components
This selectivity is achieved by the action of the glomerular filtration barrier, which comprises the glomerular basement membrane, glomerular endothelial cells and glomerular epithelial cells—or podocytes[1]
Differentiated epithelial cells, podocytes are critical in preventing protein passage across the filtration barrier
Summary
F1000 Faculty Reviews are written by members of the prestigious F1000 Faculty. They are commissioned and are peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. The reviewers who approved the final version are listed with their names and affiliations. Any comments on the article can be found at the end of the article
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