Role of Hif2α oxygen sensing pathway in bronchial epithelial club cell proliferation

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Show simple item record Torres-Capelli, Mar Marsboom, Glenn Yang Li, Qilong Oscar Tello, Daniel Melendez Rodriguez, Florinda Alonso, Tamara Sánchez-Madrid, Francisco García-Río, Francisco Ancochea, Julio Aragonés, Julián Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ) es_ES Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-IP) es_ES
dc.contributor.other UAM. Departamento de Bioquímica es_ES
dc.contributor.other UAM. Departamento de Medicina es_ES 2017-04-18T17:18:29Z 2017-04-18T17:18:29Z 2016-05-06
dc.identifier.citation Scientific Reports 6 (2016): 25357 es_ES
dc.identifier.issn 2045-232 es_ES
dc.description.abstract 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 2α (HIF2α), which controls the expression of FoxM1, a recognized proliferative factor of Club cells. Furthermore, HIF2α induced the expression of the resistin-like molecules α and β (RELMα and β), previously considered bronchial epithelial growth factors. Importantly, despite the central role of HIF2α, 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 HIF2α and Club cell biology that can be regarded as a new HIF2α-dependent mechanism involved in bronchial epithelium adaptation to oxygen fluctuations. es_ES
dc.description.sponsorship This work was supported by grants from Ministerio de Economia y Competitividad (SAF2013-46058-R), Comunidad de Madrid/Fondo Social Europeo (S2010/BMD-2542 “Consepoc-CM”) and Red de Cardiovascular (RD12/0042/0065). es_ES
dc.format.extent 10 pag es_ES
dc.format.mimetype application/pdf es_ES
dc.language.iso eng es_ES
dc.publisher Nature Publishing Group es_ES
dc.relation.ispartof Scientific Reports es_ES
dc.subject.other Oxygen-sensing es_ES
dc.subject.other HIFs es_ES
dc.subject.other Hypoxia es_ES
dc.subject.other Factor of Club cells es_ES
dc.subject.other Bronchial epithelium es_ES
dc.title Role of Hif2α oxygen sensing pathway in bronchial epithelial club cell proliferation es_ES
dc.type article es_ES
dc.subject.eciencia Medicina es_ES
dc.relation.publisherversion es_ES
dc.identifier.doi 10.1038/srep25357 es_ES
dc.identifier.publicationfirstpage 25357-1 es_ES
dc.identifier.publicationissue 6 es_ES
dc.identifier.publicationlastpage 25357-10 es_ES
dc.relation.projectID Gobierno de España. SAF2013-46058-R es_ES
dc.relation.projectID Comunidad de Madrid. S2010/BMD-2542/CONSEPOC es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES Reconocimiento es_ES
dc.rights.accessRights openAccess es_ES
dc.authorUAM Meléndez Rodríguez, Florinda Del Coral (271150)
dc.authorUAM Yang Li, Qilong Oscar (265103)
dc.authorUAM Sánchez Madrid, Francisco (259404)

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