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This study was to define whether <jats:styled-content style=\"fixed-case\"><jats:roman>Zn<\/jats:roman><\/jats:styled-content> statues (deficiency or supplement) affect the Nrf2 expression and function, and also affect the damage severity of human renal tubular (<jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>11) cells exposed to high glucose (<jats:styled-content style=\"fixed-case\">HG<\/jats:styled-content>) with palmitate (Pal) and kidney of diabetic mice induced by multiple low\u2010dose streptozotocins. For <jats:styled-content style=\"fixed-case\"><jats:roman>Zn<\/jats:roman><\/jats:styled-content> deficiency diabetic mice were treated with <jats:styled-content style=\"fixed-case\"><jats:roman>Zn<\/jats:roman><\/jats:styled-content> chelator <jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content> at 5\u00a0mg\/kg bw daily for 4\u00a0months. Results showed that <jats:styled-content style=\"fixed-case\">HG<\/jats:styled-content>\/Pal significantly increased the expression of pro\u2010fibrotic mediators, connective tissue growth factor and <jats:styled-content style=\"fixed-case\">PAI<\/jats:styled-content>\u20101, in <jats:styled-content style=\"fixed-case\">HK<\/jats:styled-content>11 cells, which was exacerbated by <jats:styled-content style=\"fixed-case\">TPEN<\/jats:styled-content> that depleted intracellular free <jats:styled-content style=\"fixed-case\"><jats:roman>Zn<\/jats:roman><\/jats:styled-content> and decreased Nrf2 expression and transcription. <jats:styled-content style=\"fixed-case\"><jats:roman>Zn<\/jats:roman><\/jats:styled-content> supplement prevented the effects of <jats:styled-content style=\"fixed-case\">TPEN<\/jats:styled-content> and also increased Akt and <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>\u20103\u03b2 phosphorylation with a decrease in Nrf2 nuclear exporter, Fyn. All these effects of <jats:styled-content style=\"fixed-case\"><jats:roman>Zn<\/jats:roman><\/jats:styled-content> were abolished by Akt inhibitor. Therefore, <jats:styled-content style=\"fixed-case\"><jats:roman>Zn<\/jats:roman><\/jats:styled-content> up\u2010regulates Nrf2 function <jats:italic>via<\/jats:italic> activating Akt\u2010mediated inhibition of Fyn function. Treatment of diabetic mice with <jats:styled-content style=\"fixed-case\">TPEN<\/jats:styled-content> decreased renal <jats:styled-content style=\"fixed-case\"><jats:roman>Zn<\/jats:roman><\/jats:styled-content> level and Nrf2 expression and transcription, with an exacerbation of renal oxidative damage, inflammation and fibrosis. These results suggest the essentiality of <jats:styled-content style=\"fixed-case\"><jats:roman>Zn<\/jats:roman><\/jats:styled-content> for Nrf2 expression and transcription function.<\/jats:p>","DOI":"10.1111\/jcmm.12239","type":"journal-article","created":{"date-parts":[[2014,3,6]],"date-time":"2014-03-06T07:12:44Z","timestamp":1394089964000},"page":"895-906","source":"Crossref","is-referenced-by-count":120,"title":["Zinc is essential for the transcription function of Nrf2 in human renal tubule cells <i>in vitro<\/i> and mouse kidney <i>in vivo<\/i> under the diabetic condition"],"prefix":"10.1111","volume":"18","author":[{"given":"Bing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Nephrology The Second Hospital of Jilin University Changchun China"},{"name":"Kosair Children's Hospital Research Institute, and Departments of Pediatrics and Pharmacology and Toxicology University of Louisville Louisville KY USA"},{"name":"Department of Nephrology Jilin Province 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