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.
Simon Livermore and Jie Pan contributed equally with all other contributors.
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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.
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Livermore, S., Pan, J., Yeger, H., Ratcliffe, P., Bishop, T., Cutz, E. (2015). Augmented 5-HT Secretion in Pulmonary Neuroepithelial Bodies from PHD1 Null Mice. In: Peers, C., Kumar, P., Wyatt, C., Gauda, E., Nurse, C., Prabhakar, N. (eds) Arterial Chemoreceptors in Physiology and Pathophysiology. Advances in Experimental Medicine and Biology, vol 860. Springer, Cham. https://doi.org/10.1007/978-3-319-18440-1_35
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DOI: https://doi.org/10.1007/978-3-319-18440-1_35
Publisher Name: Springer, Cham
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