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Nat Commun January 1, 2016; 7 12652.

The aryl hydrocarbon receptor controls cyclin O to promote epithelial multiciliogenesis.

Villa M , Crotta S , Dingwell KS , Hirst EM , Gialitakis M , Ahlfors H , Smith JC , Stockinger B , Wack A .

Epithelia function as barriers against environmental insults and express the transcription factor aryl hydrocarbon receptor (AhR). However, AhR function in these tissues is unknown. Here we show that AhR regulates multiciliogenesis in both murine airway epithelia and in Xenopus laevis epidermis. In air-exposed airway epithelia, induction of factors required for multiciliogenesis, including cyclin O (Ccno) and Multicilin (Mcidas), is AhR dependent, and air exposure induces AhR binding to the Ccno promoter. Submersion and hypoxic conditions impede AhR-dependent Ccno induction. This is mediated by the persistence of Notch signalling, as Notch blockade renders multiciliogenesis and Ccno induction by AhR independent from air exposure. In contrast to Ccno induction, air exposure does not induce the canonical AhR target cytochrome P450 1a1 (Cyp1a1). Inversely, exposure to AhR ligands induces Cyp1a1 but not Ccno and impeded ciliogenesis. These data indicate that AhR involvement in detoxification of environmental pollutants may impede its physiological role, resulting in respiratory pathology.

PubMed ID: 27554288
PMC ID: PMC4999520
Article link: Nat Commun
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: ahr ccno ctrl cyp1a1 cyp4b1 foxj1.2 hprt1 mcidas notch1

Article Images: [+] show captions
References [+] :
, Health effects of outdoor air pollution. Committee of the Environmental and Occupational Health Assembly of the American Thoracic Society. 1996, Pubmed