August 22, 2023. Blocking the Mineralocorticoid Receptor Reduces Podocyte Injury

Article name: NLRP3 Inflammasome Activation Contributes to Aldosterone-induced Podocyte Injury

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DOI

This article was published in the American Journal of Renal Physiology in 2017. It describes a study that presented new evidence that activation of NLRP3 inflammasome could be of great importance in generating podocyte damage. Thus inhibition of NLRP3 inflammasome might be an effective method for the prevention and treatment of entities that affect the podocyte and manifest as proteinuria.

In vitro, exposure of podocytes to aldosterone (mineralocorticoid receptor activation) enhanced NLRP3, caspase-1, and IL-18 expressions in dose- and time-dependent manners, indicating an activation of NLRP3 inflammasome, which was significantly blocked by the mineralocorticoid receptor antagonist eplerenone.

Overactivation of the mineralocorticoid receptor (MR) increases the expression of target genes, which are implicated in inflammatory, oxidative stress and fibrotic pathways. Ref

The MR is expressed in many types of cells, including endothelial cells, vascular smooth muscle cells, fibroblasts, macrophages, mesangial cells, and podocytes. Ref

The NLRP3 inflammasome is a multimeric protein complex that initiates an inflammatory form of cell death and triggers the release of proinflammatory cytokines IL-1β and IL-18. Ref

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