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 integrity and the secretion of cytokines such as IL-1β. However, gasdermins are now recognized as the principal effectors of this regulated cell death; activated gasdermins insert into cell membranes, forming pores that result in the secretion of cytokines, alarmins and damage-associated molecular patterns and cause cell membrane rupture. 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. In addition, the well-documented roles of inflammasome activity and apoptosis pathways in kidney diseases suggest that gasdermins and pyroptosis may be involved to some extent. However, despite some evidence for the involvement of pyroptosis in acute kidney injury and chronic kidney disease, understanding of gasdermin biology and pyroptosis in the kidney remains limited.