Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
College of Animal Science and Technology, Inner Mongolia University for Nationalities, 028000 Tongliao, China.
J Agric Food Chem. 2022 Oct 26;70(42):13765-13777. doi: 10.1021/acs.jafc.2c05816. Epub 2022 Oct 14.
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.
T-2 毒素可导致肾脏纤维化。当 Wnt/β-catenin 信号持续激活时，会促进肾脏纤维化。然而，T-2 诱导的肾脏纤维化是否涉及 Wnt/β-catenin 信号的激活尚未得到探索。T-2 毒素可导致肾脏线粒体损伤，从而导致线粒体活性氧（mtROS）过度产生和 NLRP3 炎症小体的激活。激活的 NLRP3 炎症小体可介导纤维化。然而，NLRP3 炎症小体是否可通过 mtROS 进一步通过 Wnt/β-catenin 信号调节 T-2 诱导的肾脏纤维化尚不清楚。在本研究中，首先，我们证实 T-2 毒素可在小鼠肾脏和 HK-2 细胞中引起 Wnt/β-catenin 信号的激活。其次，我们证实 mtROS 可在 T-2 暴露的小鼠肾脏和 HK-2 细胞中激活 NLRP3 炎症小体。第三，我们证实 NLRP3 炎症小体可调节 T-2 毒素暴露的小鼠肾脏和 HK-2 细胞中的 Wnt/β-catenin 信号。最后，我们证实 Wnt/β-catenin 信号可调节 T-2 毒素暴露的小鼠肾脏和 HK-2 细胞中的纤维化。上述结果证实 T-2 毒素通过 mtROS-NLRP3-Wnt/β-catenin 轴诱导肾脏纤维化。
