mTOR-Mediated Autophagy Regulates Cadmium-Induced Kidney Injury via Pyroptosis

作者：Yuan Hu, Kui Wang, Jie Xu, Guohuan Wan, Yiyi Zhao, Yajing Chen, Kangfeng Jiang, Xiaobing Li · 发表于：International Journal of Molecular Sciences · 年份：2025 · DOI：10.3390/ijms26062589 · 被引用次数：6 · 研究领域：Inflammasome and immune disorders、Heme Oxygenase-1 and Carbon Monoxide、Heavy Metal Exposure and Toxicity

The heavy metal cadmium (Cd) affects the global livestock production economy mainly through the contamination of feed raw materials and secondary contamination in feed processing, and it also poses a serious threat to food safety and human health. The nucleotide-binding oligomerization domain-like pyrin-domain-containing protein 3 (NLRP3) inflammasome is a key regulatory element of pyroptosis, which is engaged in kidney injury. Meanwhile, autophagy is also involved in renal inflammation. Mammalian target of rapamycin (mTOR) plays an important role in pyroptosis and autophagy, but its function in Cd-induced kidney injury remains unclear. In this study, we explored the role of mTOR-mediated autophagy and pyroptosis in kidney injury caused by Cd exposure and elucidated its underlying mechanism. Our data showed that Cd exposure reduced the integrity of kidney cell membranes, increased the expression of pyroptosis-associated proteins, and promoted the release of inflammatory cytokines. Subsequently, a notable attenuation in Cd-induced pyroptosis was observed following the administration of CY-09, an NLRP3 inhibitor. In addition, Cd exposure promoted autophagy in kidney cells. Importantly, in both in vivo and in vitro experiments, rapamycin, an mTOR inhibitor, downregulated the expression of pyroptosis-related proteins, thereby significantly improving Cd-induced kidney injury. In summary, our results indicate that mTOR-mediated autophagy has a significant protective effect on NLRP3...