Gasdermins and pyroptosis in the kidney

Pyroptosis is a form of regulated cell death that is mediated by the membrane-targeting, pore-forming gasdermin family of proteins. Pyroptosis was initially described as a caspase 1-and inflammasome-dependent cell death pathway typified by the loss of membrane integ-rity and the secretion of cytokines such as IL-1 beta. However, gasdermins are now recognized as the principal effectors of this form of regulated cell death; activated gasdermins insert into cell membranes, where they form pores that result in the secretion of cytokines, alarmins and damage-associated molecular patterns and cause cell membrane rupture. It is now evident that gasdermins can be activated by inflamma- some-and caspase-independent mechanisms in multiple cell types and that crosstalk occurs between pyroptosis and other cell death pathways. Although they are important for host antimicrobial defence, a growing body of evidence supports the notion that pyroptosis and gasdermins have pathological roles in cancer and several non-microbial diseases involving the gut, liver and skin. The well-documented roles of inflammasome activity and apoptosis pathways in kidney diseases suggests that gasdermins and pyroptosis may also be involved to some extent. However, despite some evidence for involvement of pyroptosis in the context of acute kidney injury and chronic kidney disease, our understanding of gasdermin biology and pyroptosis in the kidney remains limited.