Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang 330045, Jiangxi, PR China.
Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang 330045, Jiangxi, PR China.
J Hazard Mater. 2024 Dec 5;480:135904. doi: 10.1016/j.jhazmat.2024.135904. Epub 2024 Sep 18.
Vanadium (V) is a poisonous metallic environmental pollutant which poses hazard to the animal health of the liver. Competitive endogenous ribonucleic acids (ceRNAs) are essential elements of mitochondrial function and apoptosis, and their effects have been associated with the metal toxicity mechanism. However, the specific mechanism of ceRNAs in V-induced mitochondrial apoptosis in the liver has not been adequately investigated. Hence, we established an in vivo model of ducks exposed to V for 44 days and an in vitro model of V exposure duck hepatocyte knockdown/overexpression. Results showed that V exposure triggered the differential expression of 1106 lncRNAs and 11 miRNAs in the liver. Besides, we established the lncRNA-00742/miR-116/CD74 regulatory network by the dual luciferase reporter gene. Our results also found that V induced mitochondrial injury and up-regulated the expression levels of mitochondrial apoptosis-related factors. Furthermore, knockdown of miR-116 attenuated V-induced mitochondrial injury and apoptosis in hepatocytes. In contrast, overexpression of miR-116 and knockdown of CD74 exacerbated mitochondrial injury and apoptosis. BTZO-1 upregulated the CD74 level and alleviated V-induced mitochondrial apoptosis. In summary, V induced mitochondrial damage and apoptosis in duck liver by activating the lncRNA-00742/miR-116/CD74 axis. This research firstly revealed the mechanism of lncRNA-related ceRNAs regulating V-induced mitochondrial apoptosis.
钒（V）是一种有毒的金属环境污染物，对肝脏的动物健康构成危害。竞争性内源性核糖核酸（ceRNA）是线粒体功能和细胞凋亡的重要组成部分，它们的作用与金属毒性机制有关。然而，ceRNA 在 V 诱导的肝脏线粒体细胞凋亡中的具体机制尚未得到充分研究。因此，我们建立了一个暴露于 V 44 天的鸭体内模型和一个 V 暴露鸭肝细胞敲低/过表达的体外模型。结果表明，V 暴露触发了肝脏中 1106 个 lncRNA 和 11 个 miRNA 的差异表达。此外，我们通过双荧光素酶报告基因建立了 lncRNA-00742/miR-116/CD74 调控网络。我们的结果还发现，V 诱导线粒体损伤并上调线粒体凋亡相关因子的表达水平。此外，miR-116 的敲低减轻了 V 诱导的肝细胞线粒体损伤和凋亡。相比之下，miR-116 的过表达和 CD74 的敲低加剧了线粒体损伤和凋亡。BTZO-1 上调 CD74 水平并减轻 V 诱导的线粒体凋亡。总之，V 通过激活 lncRNA-00742/miR-116/CD74 轴诱导鸭肝线粒体损伤和凋亡。这项研究首次揭示了 lncRNA 相关 ceRNA 调节 V 诱导的线粒体细胞凋亡的机制。
