The aryl hydrocarbon receptor controls cyclin O to promote epithelial multiciliogenesis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-08-24

AUTHORS

Matteo Villa, Stefania Crotta, Kevin S Dingwell, Elizabeth M A Hirst, Manolis Gialitakis, Helena Ahlfors, James C Smith, Brigitta Stockinger, Andreas Wack

ABSTRACT

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. More... »

PAGES

12652

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms12652

DOI

http://dx.doi.org/10.1038/ncomms12652

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039363170

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27554288


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