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 toxin treatment causes male reproduction system dysfunction,
although the exact mechanism remains unclear. In this research, male
Kunming mice and TM4 cells were treated with varying concentrations
of the T-2 toxin for evaluating the adverse effect of T-2 toxin on
male reproductive function. MCC950 or NAC was used to block NLRP3
inflammasome activation and eliminate reactive oxygen species (ROS)
accumulation in the TM4 cell, respectively. The results showed that:
(1) T-2 toxin caused testicular atrophy, destroyed the microstructure
and ultrastructure of the testis, and caused sperm deformities; (2)
T-2 toxin increased the content and gene expressions of TNF-α
and IL-6 and decreased the IL-10 content and gene expression, causing
testis and TM4 cell inflammatory injury; (3) T-2 toxin activated NLRP3
inflammasome in the testis and TM4 cells and caused ROS accumulation
in the testis; (4) suppressing NLRP3 inflammasome activation using
20 nM MCC950 alleviated the TM4 cell inflammatory damage caused via
the T-2 toxin; nevertheless, 20 nM MCC950 did not reduce ROS accumulation
in TM4 cells; and (5) NAC relieved the inflammatory damage in TM4
cells by inhibiting NLRP3 inflammasome activation. Taken together,
T-2 toxin caused testicular inflammation injury through ROS-mediated
NLRP3 inflammasome activation, resulting in male reproductive dysfunction.
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