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Augmented 5-HT Secretion in Pulmonary Neuroepithelial Bodies from PHD1 Null Mice

  • Simon Livermore
  • Jie Pan
  • Herman Yeger
  • Peter Ratcliffe
  • Tammie Bishop
  • Ernest CutzEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 860)

Abstract

Sustained exposure to low oxygen concentration leads to profound changes in gene expression to restore oxygen homeostasis. Hypoxia-inducible factors (HIFs) comprise a group of transcription factors which accumulate under hypoxia and contribute to the complex changes in gene expression. Under normoxic conditions HIFs are degraded by prolyl-hydroxylases (PHD), however during hypoxia this degradation is inhibited causing HIF accumulation and subsequent changes in gene expression. Pulmonary neuroepithelial bodies (NEB) are innervated serotonin (5-HT)-producing cells distributed throughout the airway epithelium. These putative O2 sensors are hypothesized to contribute to the ventilatory response to hypoxia. NEB dysfunction has been implicated in several paediatric lung diseases including neuroendocrine cell hyperplasia of infancy and sudden infant death syndrome, both characterized by a marked NEB hyperplasia with unknown functional significance. We have previously reported striking NEB hyperplasia in PHD1−/− mice making these mice a potential model to study the role of NEBs in paediatric lung diseases. Here we report in vitro studies on 5-HT release from NEB using this model.

Keywords

Airway oxygen sensors Hypoxia signalling Pulmonary neuroendocrine cell hyperplasia Paediatric lung disease 

Notes

Acknowledgements

Supported by grants from Canadian Institute for Health Research (MOP 15270) to EC and H.Y., and welcome trust (Programme grant #091857) to P.R. and T.B.

References

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Simon Livermore
    • 1
  • Jie Pan
    • 1
  • Herman Yeger
    • 1
  • Peter Ratcliffe
    • 2
  • Tammie Bishop
    • 2
  • Ernest Cutz
    • 1
    Email author
  1. 1.Division of Pathology, Department of Pediatric Laboratory Medicine, The Research Institute, The Hospital for Sick Children and Department of Laboratory Medicine and PathobiologyUniversity of TorontoTorontoCanada
  2. 2.The Henry Wellcome Building for Molecular PhysiologyUniversity of OxfordOxfordUK

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