The Role And Mechanism Of NALP3Inflammsome Activation In Podocyte Injury Of Diabetic Nephropathy

Numerous studies have shown that NALP3inflammasome plays an important role in various immunity and inflammation-mediated diseases. However, whether NALP3inflammasome is involved in podocyte injury of diabetic nephropathy (DN) is still unclear. In our study, we confirmed that high glucose (HG) induced NALP3inflammasome activation in vivo and in vitro. Inhibition of NALP3inflammasome expression or caspase-1activity prevented NALP3inflammasome activation, IL-1β production and eventually attenuated podocyte and glomerulus injury in HG condition in vivo and in vitro. It is also found that thioredoxin(TRX)-interacting protein(TXNIP), a pro-oxidative stress and pro-inflammatory factor could activate NALP3inflammasome by NADPH oxidase(gp91phox) depended reactive oxygen species(ROS) generation. Suppression of TXNIP and gp91phox all impeded NALP3inflammasome activation and attenuated podocyte injury induced by HG. In summary, NALP3inflammasome mediates podocyte and glomerulus injury in DN. Moreover, our study for the first time links TXNIP and gp91phox to the formation and activation of NALP3inflammasome in podocytes during DN, which represents a novel mechanism of diabetes-associated podocyte and glomerular injury.