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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 inflammasome-dependent kidney injury induced by Cd exposure, thus providing new insights into the prevention and treatment of Cd poisoning.<\/jats:p>","DOI":"10.3390\/ijms26062589","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T06:53:00Z","timestamp":1741848780000},"page":"2589","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["mTOR-Mediated Autophagy Regulates Cadmium-Induced Kidney Injury via Pyroptosis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2843-534X","authenticated-orcid":false,"given":"Yuan","family":"Hu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohuan","family":"Wan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyi","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangfeng","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobing","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134499","DOI":"10.1016\/j.snb.2023.134499","article-title":"An ICT-based ratiometric fluorescent probe for tracking and imaging SO2 during Cd-induced stress in plants","volume":"395","author":"Zhang","year":"2023","journal-title":"Sens. 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