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Role of actin cytoskeleton in podocytes

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Abstract

The selectivity of the glomerular filter is established by physical, chemical, and signaling interplay among its three core constituents: glomerular endothelial cells, the glomerular basement membrane, and podocytes. Functional impairment or injury of any of these three components can lead to proteinuria. Podocytes are injured in many forms of human and experimental glomerular disease, including minimal change disease, focal segmental glomerulosclerosis, and diabetes mellitus. One of the earliest signs of podocyte injury is loss of their distinct structure, which is driven by dysregulated dynamics of the actin cytoskeleton. The status of the actin cytoskeleton in podocytes depends on a set of actin binding proteins, nucleators and inhibitors of actin polymerization, and regulatory GTPases. Mutations that alter protein function in each category have been implicated in glomerular diseases in humans and animal models. In addition, a growing body of studies suggest that pharmacological modifications of the actin cytoskeleton have the potential to become novel therapeutics for podocyte-dependent chronic kidney diseases. This review presents an overview of the essential proteins that establish actin cytoskeleton in podocytes and studies demonstrating the feasibility of drugging actin cytoskeleton in kidney diseases.

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  1. Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA

    Sanja Sever

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S. S. is the co-founder and shareholder of Trisaq, a biotechnology company that develops novel kidney-protective therapies.

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Sever, S. Role of actin cytoskeleton in podocytes. Pediatr Nephrol 36, 2607–2614 (2021). https://doi.org/10.1007/s00467-020-04812-z

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