MicroRNA-223 downregulation promotes HBx-induced podocyte pyroptosis by targeting the NLRP3 inflammasome

Abstract

Hepatitis B virus (HBV) and its related protein, HBV X (HBx), play an important role in podocyte injury in HBV-associated glomerulonephritis (HBV-GN). The microRNA MiR-223 is expressed in several diseases, including HBV-associated disease, while the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a major role in pyroptosis. In this study, we investigated the function and mechanism of action of miR-223 in HBx-induced podocyte pyroptosis. A quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) assay showed that miR-223 was downregulated in HBx-transfected podocytes. Transfection with an miR-223 mimic abolished the expression of the NLRP3 inflammasome and the cytokines that are released as a result of NLRP3 overexpression. Moreover, transfection with HBx and NLRP3 overexpression plasmids increased the expression of pyroptosis-related proteins, especially in the presence of miR-223 inhibitors. Thus, miR-223 downregulation plays an important role in HBx-induced podocyte pyroptosis by targeting the NLRP3 inflammasome, suggesting that miR-223 is a potential therapeutic target for alleviating HBV-GN inflammation.