| First Author | Torres-Capelli M | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 25357 | PubMed ID | 27150457 |
| Mgi Jnum | J:253838 | Mgi Id | MGI:6102619 |
| Doi | 10.1038/srep25357 | Citation | Torres-Capelli M, et al. (2016) Role Of Hif2alpha Oxygen Sensing Pathway In Bronchial Epithelial Club Cell Proliferation. Sci Rep 6:25357 |
| abstractText | Oxygen-sensing pathways executed by the hypoxia-inducible factors (HIFs) induce a cellular adaptive program when oxygen supply becomes limited. However, the role of the HIF oxygen-sensing pathway in the airway response to hypoxic stress in adulthood remains poorly understood. Here we found that in vivo exposure to hypoxia led to a profound increase in bronchial epithelial cell proliferation mainly confined to Club (Clara) cells. Interestingly, this response was executed by hypoxia-inducible factor 2alpha (HIF2alpha), which controls the expression of FoxM1, a recognized proliferative factor of Club cells. Furthermore, HIF2alpha induced the expression of the resistin-like molecules alpha and beta (RELMalpha and beta), previously considered bronchial epithelial growth factors. Importantly, despite the central role of HIF2alpha, this proliferative response was not initiated by in vivo Vhl gene inactivation or pharmacological inhibition of prolyl hydroxylase oxygen sensors, indicating the molecular complexity of this response and the possible participation of other oxygen-sensing pathways. Club cells are principally involved in protection and maintenance of bronchial epithelium. Thus, our findings identify a novel molecular link between HIF2alpha and Club cell biology that can be regarded as a new HIF2alpha-dependent mechanism involved in bronchial epithelium adaptation to oxygen fluctuations. |
