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Podocyte Rho GTPases: new therapeutic targets for Nephrotic Syndrome?

Research output: Contribution to journalReview article

Original languageEnglish
Number of pages6
JournalF1000Research
DOIs
DateAccepted/In press - 4 Oct 2019
DatePublished (current) - 4 Nov 2019

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.

    Research areas

  • Podocyte, RhoGTPases, Nephrotic Syndrome

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via F1000Research at https://f1000research.com/articles/8-1847. Please refer to any applicable terms of use of the publisher.

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    Licence: CC BY

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