The aryl hydrocarbon receptor controls cyclin O to promote epithelial multiciliogenesis
| Autor: | Elizabeth M. A. Hirst, Brigitta Stockinger, Stefania Crotta, Matteo Villa, Andreas Wack, Helena Ahlfors, Kevin S. Dingwell, James C. Smith, Manolis Gialitakis |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Science Xenopus Notch signaling pathway General Physics and Astronomy Cell Cycle Proteins Respiratory Mucosa Biology Xenopus Proteins Bioinformatics General Biochemistry Genetics and Molecular Biology Article Animals Genetically Modified 03 medical and health sciences Mice Xenopus laevis Ciliogenesis Cyclins Basic Helix-Loop-Helix Transcription Factors Cytochrome P-450 CYP1A1 Animals RNA Messenger Receptor Promoter Regions Genetic Transcription factor Cells Cultured Cyclin Regulation of gene expression Mice Knockout Air Pollutants Multidisciplinary Nuclear Proteins General Chemistry respiratory system Aryl hydrocarbon receptor biology.organism_classification 3. Good health Cell biology respiratory tract diseases Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation Receptors Aryl Hydrocarbon 13. Climate action Inactivation Metabolic biology.protein Epidermis |
| Zdroj: | Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-11 (2016) |
| ISSN: | 2041-1723 |
| Popis: | 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. Epithelia are barriers against environmental insults and express the transcription factor aryl hydrocarbon receptor (AhR). Here the authors show that AhR regulates multiciliogenesis via cyclin O and Multicilin in a Notch-dependent manner and that this is blocked by toxic ligands. |
| Databáze: | OpenAIRE |
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