MiR-196a regulates heme oxygenase-1 by silencing Bach1 in the neonatal mouse lung

Hayato Go, Ping La, Fumihiko Namba, Masato Ito, Guang Yang, Andrey Brydun, Kazuhiko Igarashi, Phyllis A. Dennery

研究成果: Article査読

19 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)400-411
ページ数12
ジャーナルAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
311
2
DOI
出版ステータスPublished - 2016 8月 1
外部発表はい

ASJC Scopus subject areas

  • 生理学
  • 呼吸器内科
  • 生理学(医学)
  • 細胞生物学

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