Podocyte as the link between sterile inflammation and diabetic kidney disease

Abstract

Shahzad et al. examined the underlying mechanisms of sterile inflammation in diabetic kidney disease, specifically the role of NLRP3 inflammasome activation in podocytes. Using mouse models with gain-of-function and loss-of-function mutations in podocyte Nlrp3, or caspase-1 loss-of-function mutations in podocytes, they identified that Nlrp3 activation in these cells is central for development of diabetic kidney disease but not solely dependent on canonical mechanisms and caspase-1. These findings position podocyte-mediated immune cell-like functions as potential therapeutic targets for diabetic kidney disease.

Figure 1 |. Podocyte NLRP3 inflammasome activation in diabetic kidney disease (DKD).

Podocyte injury and depletion are features of DKD. Shahzad et al. showed that activating the NLRP3 inflammasome in podocytes results in the release of interleukin (IL)-1β and leads to podocyte and glomerular injury in diabetic mice. Inhibition of canonical and noncanonical NLRP3 inflammasome pathways with small molecules (e.g., MCC950) or induction of autophagy to inhibit inflammasome activation (e.g., CB2R agonists) could be potential therapeutic strategies to prevent sterile inflammation in DKD. N-GSDMD, N-gasdermin-D fragments.