{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T18:28:58Z","timestamp":1793557738454,"version":"4.5.0"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2017,11,10]],"date-time":"2017-11-10T00:00:00Z","timestamp":1510272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015502","name":"Dialysis Clinic, Inc.","doi-asserted-by":"publisher","award":["DCI#C-3917"],"award-info":[{"award-number":["DCI#C-3917"]}],"id":[{"id":"10.13039\/100015502","id-type":"DOI","asserted-by":"publisher"}]},{"name":"California TRDRP","award":["#23FT-0104"],"award-info":[{"award-number":["#23FT-0104"]}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["T32 HL007013-35 and R01 HL096373"],"award-info":[{"award-number":["T32 HL007013-35 and R01 HL096373"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cigarette smoke has been shown to trigger aberrant signaling pathways and pathophysiological processes; however, the regulatory mechanisms underlying smoke-induced gene expression remain to be established. Herein, we observed that two smoke-responsive genes, HO-1 and CYP1A1, are robustly induced upon smoke by different mechanisms in human bronchial epithelia. CYP1A1 is mediated by aryl hydrocarbon receptor signaling, while induction of HO-1 is regulated by oxidative stress, and suppressed by N-acetylcysteine treatment. In light of a pivotal role of NRF2 and BACH1 in response to oxidative stress and regulation of HO-1, we examined if smoke-induced HO-1 expression is modulated through the NRF2\/BACH1 axis. We demonstrated that smoke causes significant nuclear translocation of NRF2, but only a slight decrease in nuclear BACH1. Knockdown of NRF2 attenuated smoke-induced HO-1 expression while down-regulation of BACH1 had stimulatory effects on both basal and smoke-induced HO-1 with trivial influence on NRF2 nuclear translocation. Chromatin immunoprecipitation assays showed that smoke augments promoter-specific DNA binding of NRF2 but suppresses BACH1 binding to the HO-1 promoter ARE sites, two of which at \u22121.0 kb and \u22122.6 kb are newly identified. These results suggest that the regulation of NRF2 activator and BACH1 repressor binding to the ARE sites are critical for smoke-mediated HO-1 induction.<\/jats:p>","DOI":"10.3390\/ijms18112386","type":"journal-article","created":{"date-parts":[[2017,11,10]],"date-time":"2017-11-10T11:12:26Z","timestamp":1510312346000},"page":"2386","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cigarette Smoke Regulates the Competitive Interactions between NRF2 and BACH1 for Heme Oxygenase-1 Induction"],"prefix":"10.3390","volume":"18","author":[{"given":"Wen-Hsin","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine and Center for Comparative Respiratory Biology and Medicine, University of California Davis, Davis, CA 95616, USA"},{"name":"Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Thai","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine and Center for Comparative Respiratory Biology and Medicine, University of California Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4063-0608","authenticated-orcid":false,"given":"Jihao","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of California Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine and Center for Comparative Respiratory Biology and Medicine, University of California Davis, Davis, CA 95616, USA"},{"name":"Division of Nephrology, Department of Internal Medicine, University of California Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine and Center for Comparative Respiratory Biology and Medicine, University of California Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Hsien","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of California Davis, Davis, CA 95616, USA"},{"name":"Comprehensive Cancer Center, University of California Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.rmed.2011.11.003","article-title":"The effects of cigarette smoke on airway inflammation in asthma and COPD: Therapeutic implications","volume":"106","author":"Tamimi","year":"2012","journal-title":"Respir. 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