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ZRT\/IRT-like protein 14 (ZIP14) is a transport protein that can mediate cellular uptake of iron, zinc, and manganese. Herein, we have tested the hypothesis that the divalent metal transporter ZIP14 is involved in the initiation of ferroptosis in diabetic nephropathy (DN). DN was induced in 8-week-old male rats by streptozotocin before analysis of the degree of renal tubular injury. In addition, an in vitro model of DN in human kidney proximal tubular cell line was used. We showed that ZIP14 was up-regulated and ferrous iron (Fe2+) levels increased both in vivo and in vitro. Expression of glutathione\u00a0peroxidase\u00a04 and the level of glutathione were reduced, whereas that of malondialdehyde (MDA) increased. Ferrostatin-1 (Fer-1) treatment reduced the expression of ZIP14 and the levels of Fe2+ and MDA, which is consistent with ferroptosis. Fer-1 improved kidney function in DN rats. This was characterized by urine levels of protein-to-creatinine ratio, \u03b11-microglobulin, and N-acetyl-\u03b2-D-glucosaminidase. Our study demonstrates a novel role for ZIP14 in diabetic kidney injury mediated by ferroptosis, and suggests a potential new therapeutic approach for the treatment of diabetic nephropathy.<\/jats:p>","DOI":"10.1093\/mtomcs\/mfac034","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T01:16:52Z","timestamp":1654046212000},"source":"Crossref","is-referenced-by-count":63,"title":["ZIP14 is involved in iron deposition and triggers ferroptosis in diabetic nephropathy"],"prefix":"10.1093","volume":"14","author":[{"given":"Keping","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Nephrology, Kidney and Urology Center, The Seventh Affiliated Hospital of Sun Yat-Sen University , Shenzhen, China"},{"name":"Department of Nephrology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University , Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyan","family":"Fei","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kidney and Urology Center, The Seventh Affiliated Hospital of Sun Yat-Sen University , Shenzhen, China"},{"name":"Institute of Translation Physiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt\u2014Universit\u00e4t zu Berlin, \u00a0 Germany"},{"name":"Department of Nephrology, The First Affiliated Hospital of Sun Yat-Sen University , Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kidney and Urology Center, The Seventh Affiliated Hospital of Sun Yat-Sen University , Shenzhen, 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