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BARD may exert its beneficial effect by increasing expression of genes previously shown to protect against ischemic AKI, NF-E2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor-\u03b3 (PPAR\u03b3), and heme oxygenase 1 (HO-1). Although we found that BARD alone or ischemia-reperfusion alone increased expression of these genes, the greatest increase occurred after the combination of both ischemia-reperfusion and BARD. BARD had a different mode of action than other agents that regulate PPAR\u03b3 and Nrf2. Thus we report that BARD regulates PPAR\u03b3, not by acting as a ligand but by increasing the amount of PPAR\u03b3 mRNA and protein. This should increase ligand-independent effects of PPAR\u03b3. Similarly, BARD increased Nrf2 mRNA; this increased Nrf2 protein by mechanisms in addition to the prolongation of Nrf2 protein half-life previously reported. Finally, we localized expression of these protective genes after ischemia and BARD treatment. Using double-immunofluorescence staining for CD31 and Nrf2 or PPAR\u03b3, we found increased Nrf2 and PPAR\u03b3 on glomerular endothelia in the cortex; Nrf2 was also present on cortical peritubular capillaries. In contrast, HO-1 was localized to different cells, i.e., tubules and interstitial leukocytes. Although Nrf2-dependent increases in HO-1 have been described, our data suggest that BARD's effects on tubular and leukocyte HO-1 during ischemic AKI may be Nrf2 independent. We also found that BARD ameliorated cisplatin nephrotoxicity.<\/jats:p>","DOI":"10.1152\/ajprenal.00353.2010","type":"journal-article","created":{"date-parts":[[2011,2,2]],"date-time":"2011-02-02T23:49:24Z","timestamp":1296690564000},"page":"F1180-F1192","source":"Crossref","is-referenced-by-count":146,"title":["Bardoxolone methyl (BARD) ameliorates ischemic AKI and increases expression of protective genes Nrf2, PPAR\u03b3, and HO-1"],"prefix":"10.1152","volume":"300","author":[{"given":"Qing Qing","family":"Wu","sequence":"first","affiliation":[{"name":"Departments of 1Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of 1Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Senitko","sequence":"additional","affiliation":[{"name":"Departments of 1Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin","family":"Meyer","sequence":"additional","affiliation":[{"name":"Reata Pharmaceuticals, Incorporated, Irving, Texas; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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