Background IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and it is characterized by mesangial IgA deposits. Proteinuria is a common clinical feature of IgAN, which has a critical connection to podocyte injury and has been used as a clinical prognostic factor for IgAN. Evidence has shown that TNF-α released from mesangial cells may lead to podocyte apoptosis. Methods Forty male BALB/c mouse were randomly divided into the control group and IgAN group. A mice model of IgAN was developed by oral administration of bovine serum albumin (BSA) combined with Staphylococcus Enterotoxin B (SEB) tail vein injection. Urinary protein concentrations, renal function, renal morphological, IgA deposition, apoptosis situation, and the mRNA and protein expression of nephrin, podocin, TNF-α, TNFR1, caspase-8 and caspase-3, were detected after 12 weeks. Results BSA and SEB can successfully establish an IgAN mouse model, and the main pathological changes are the IgA immune complex deposition in the mesangial area. The gene and protein expression levels of nephrin and podocin were found to be downregulated, and death receptor pathway-related indicators were upregulated, and they were involved in TNF-α-activated podocyte injury and apoptosis in IgAN mice. Conclusion TNF-α may play an important role in the pathogenesis of podocyte apoptosis in IgAN, and its effects may be mediated through the apoptotic death receptor pathway.

Renal injury resulting from hyperuricemia has gained a lot of interest. Pyroptosis refers to inflammatory cell death. The activated caspase-1 cleavage, and the pivotal protein - GSDMD could have an association with the hyperuricemic kidney lesion pathogenesis. ROS is a vital NLRP3 inflammasome antagonist in various cells. We investigated the mechanism through which ROS stimulates NLRP3 to modulate pyroptosis in renal tubular epithelial cells as well as hyperuricemic rat kidneys. Methods: In vitro cultured renal tubular epithelial cells（NRK-52E cells）were incubated with a gradient concentration of uric acid for 24 hr to investigate the pyroptosis through flow cytometry. Next, we used the inhibitors of ROS, mitochondrial ROS, NLRP3 and Caspase-1 respectively to intervene in uric acid treated cells to analyse pyproptosis and activation of ROS- NLRP3 inflammasome signal pathway. Finally, we evaluated the mechanism of hyperuricemia triggering renal tubular epithelial pyroptosis in rat kidney tissues. Results: The levels of ROS and mitochondrial ROS, the mRNA and protein expression of pyroptosis-associated factors Caspase-1 (p45, p20/10), NLRP3, and GSDMD were upregulated in uric acid, the induced NRK-52E cells as well as hyperuricemic model kidneys. The inhibition of ROS, mitochondrial ROS, NLRP3, or caspase-1 in the uric acid-induced NRK-52E cells may help in controlling pyroptosis. The expression of mRNA and protein by the cytokines IL-18 and IL-1β also increased. Conclusions: Generally, hyperuricemia triggered renal tubular epithelial pyroptosis via excessive ROS to modulate NLRP3 inflammasome activation in uric acid stimulated renal tubular epithelial cells as well as the oxonic acid potassium induced hyperuricemia.