title: Aryl hydrocarbon receptor (AhR)-dependent regulation of pulmonary miRNA by chronic cigarette smoke exposure.
abstract: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically known for its toxic responses to man-made pollutants such as dioxin. More recently, the AhR has emerged as a suppressor of inflammation, oxidative stress and apoptosis from cigarette smoke by mechanisms that may involve the regulation of microRNA. However, little is known about the AhR regulation of miRNA expression in the lung in response to inhaled toxicants. Therefore, we exposed Ahr-/-and Ahr+/-mice to cigarette smoke for 4 weeks and evaluated lung miRNA expression by PCR array. There was a dramatic regulation of lung miRNA by the AhR in the absence of exogenous ligand. In response to cigarette smoke, there were more up-regulated miRNA in Ahr-/-mice compared to Ahr+/-mice, including the cancer-associated miRNA miR-96. There was no significant change in the expression of the AhR regulated proteins HuR and cyclooxygenase-2 (COX-2). There were significant increases in the anti-oxidant gene sulfiredoxin 1 (Srxn1) and FOXO3a- predicted targets of miR-96. Collectively, these data support a prominent role for the AhR in regulating lung miRNA expression. Further studies to elucidate a role for these miRNA may further uncover novel biological function for the AhR in respiratory health and disease.
authors.affiliation: Departments of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rogers
authors.affiliation: Research Institute of the McGill University Health Centre (RI-MUHC), Meakins-Christie Laboratories, Montreal, QC, Canada.
authors.forename: Angela Rico
authors.initials: AR
authors.lastname: de Souza
authors.affiliation: Departments of Pharmacology &Therapeutics, McGill University, Montreal, Quebec, Canada.
authors.forename: Michela
authors.initials: M
authors.lastname: Zago
authors.affiliation: Departments of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Iu
authors.affiliation: Departments of Pathology, McGill University, Montreal, Quebec, Canada.
authors.forename: Necola
authors.initials: N
authors.lastname: Guerrina
authors.affiliation: Department of Pharmacology &Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Alvin
authors.initials: A
authors.lastname: Gomez
authors.affiliation: Department of Pharmacology &Toxicology, University of Toronto, Toronto, Ontario, Canada.|Department of Nutrition, University of Oslo, Oslo, Norway.
authors.forename: Jason
authors.initials: J
authors.lastname: Matthews
authors.affiliation: Departments of Medicine, McGill University, Montreal, Quebec, Canada.|Research Institute of the McGill University Health Centre (RI-MUHC), Meakins-Christie Laboratories, Montreal, QC, Canada.|Departments of Pharmacology &Therapeutics, McGill University, Montreal, Quebec, Canada.|Departments of Pathology, McGill University, Montreal, Quebec, Canada.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Baglole
mesh_terms: D000818:Animals; D002633:Chemotaxis / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D000067780:ELAV-Like Protein 1 / Q000235:genetics / Q000378:metabolism; D000071316:Forkhead Box Protein O3 / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D007700:Kinetics; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000172:deficiency / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics*
chemical_list: D016207:Cytokines; D000067780:ELAV-Like Protein 1; D000071316:Forkhead Box Protein O3; C474033:FoxO3 protein, mouse; D035683:MicroRNAs; D018336:Receptors, Aryl Hydrocarbon; D051546:Cyclooxygenase 2; D050862:Oxidoreductases Acting on Sulfur Group Donors; C529381:sulfiredoxin protein, mouse