title: MiR-196a regulates heme oxygenase-1 by silencing Bach1 in the neonatal mouse lung.
abstract: In the lung, heme oxygenase-1 (HO-1) is developmentally regulated, with its highest expression in the first days of life. In addition, neonatal mice have limited HO-1 induction in hyperoxia compared with adults. However, few reports have addressed the functional effect of microRNAs (miRNAs) in the regulation of HO-1 in vivo. The aims of the present study were to characterize changes in lung miRNA expression during postnatal development and in response to hyperoxic exposure, and to identify miRNAs that target lung HO-1 gene expression. Neonatal (<12 h old) and adult (2 mo old) mice were exposed to room air or hyperoxia (95% oxygen) for 72 h. TaqMan low-density array rodent miRNA assays were used to calculate miRNA expression changes between control and hyperoxia groups in neonatal and adult lungs. In neonates, we identified miR-196a, which binds to the 3'-untranslated region of the transcriptional repressor BTB and CNC homology 1 (Bach1) and regulates its expression, and subsequently leads to higher levels of lung HO-1 mRNA compared with levels in adults. Despite the increase at baseline, miR-196a was degraded in hyperoxia resulting in limited HO-1 induction in neonatal mice lungs. Furthermore, the developmental differences in lung HO-1 gene expression can be explained in part by the variation in miRNA-196a and its effect on Bach1. This report is the first to show developmental differences in lung miR-196a and its effect on Bach1 and HO-1 expression at baseline and in hyperoxia.
authors.affiliation: Department of Neonatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Pediatrics, Fukushima Medical University School of Medicine, Fukushima, Japan;
authors.forename: Hayato
authors.initials: H
authors.lastname: Go
authors.affiliation: Department of Neonatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania;
authors.forename: Ping
authors.initials: P
authors.lastname: La
authors.affiliation: Department of Neonatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Pediatrics, Saitama Medical Center, Saitama, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Namba
authors.affiliation: Department of Pediatrics, Saitama Medical Center, Saitama, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Neonatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania;
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan;
authors.forename: Andrey
authors.initials: A
authors.lastname: Brydun
authors.affiliation: Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan;
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Igarashi
authors.affiliation: Department of Neonatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania and Alpert Medical School at Brown University, Providence, Rhode Island; and phyllis_dennery@brown.edu.
authors.forename: Phyllis A
authors.initials: PA
authors.lastname: Dennery
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000831:Animals, Newborn; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D001997:Bronchopulmonary Dysplasia / Q000201:enzymology; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000201:enzymology* / Q000254:growth & development; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; C000602251:MIRN196 microRNA, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; C540674:Mirn27 microRNA, mouse; D012333:RNA, Messenger; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Bach1; HO-1; hyperoxic lung injury; lung development; microRNA-196a