T-2 Toxin Induces Kidney Fibrosis via the mtROS-NLRP3-Wnt/β-Catenin Axis.

Abstract

T-2 toxin causes kidney fibrosis. Wnt/β-catenin signaling promotes kidney fibrosis when sustained and activated. However, whether T-2-induced kidney fibrosis involves Wnt/β-catenin signaling activation has not been explored yet. T-2 toxin causes renal mitochondrial damage, leading to mitochondrial reactive oxygen species (mtROS) overproduction and NLRP3-inflammasome activation. The activated NLRP3-inflammasome can mediate fibrosis. However, whether the NLRP3-inflammasome can be mediated by mtROS and further regulate T-2-induced kidney fibrosis through Wnt/β-catenin signaling is unclear. In this study, first, we confirmed that T-2 toxin caused Wnt/β-catenin signaling activation in mice kidneys and HK-2 cells. Second, we confirmed that mtROS activated the NLRP3-inflammasome in T-2-exposed mice kidneys and HK-2 cells. Third, we confirmed that the NLRP3-inflammasome regulated the Wnt/β-catenin signaling in T-2 toxin-exposed mice kidneys and HK-2 cells. Finally, we confirmed that Wnt/β-catenin signaling regulated fibrosis in T-2 toxin-exposed mice kidneys and HK-2 cells. The above results confirm that T-2 toxin induces kidney fibrosis via the mtROS-NLRP3-Wnt/β-catenin axis.