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Authordc.contributor.authorMéndez, Andrea 
Authordc.contributor.authorRojas, Diego A. 
Authordc.contributor.authorPonce, Carolina A. 
Authordc.contributor.authorBustamante, Rebeca 
Authordc.contributor.authorBeltrán, Caroll J. 
Authordc.contributor.authorToledo, Jorge 
Authordc.contributor.authorGarcía-Angulo, Victor A. 
Authordc.contributor.authorHenriquez, Mauricio 
Authordc.contributor.authorVargas, Sergio L. 
Admission datedc.date.accessioned2019-10-30T15:40:06Z
Available datedc.date.available2019-10-30T15:40:06Z
Publication datedc.date.issued2019
Cita de ítemdc.identifier.citationPLoS ONE, Volumen 14, Issue 6, 2019,
Identifierdc.identifier.issn19326203
Identifierdc.identifier.other10.1371/journal.pone.0217684
Identifierdc.identifier.urihttps://repositorio.uchile.cl/handle/2250/172533
Abstractdc.description.abstractClara cells are the main airway secretory cells able to regenerate epithelium in the distal airways through transdifferentiating into goblet cells, a process under negative regulation of the Notch pathway. Pneumocystis is a highly prevalent fungus in humans occurring between 2 and 5 months of age, a period when airways are still developing and respiratory morbidity typically increases. Pneumocystis induces mucus hyperproduction in immunocompetent host airways and whether it can stimulate Clara cells is unknown. Markers of Clara cell secretion and Notch1 activation were investigated in lungs of immunocompetent rats at 40, 60, and 80 days of age during Pneumocystis primary infection with and without Valproic acid (VPA), a Notch inducer. The proportion of rats expressing mucin increased in Pneumocystis-infected rats respect to controls at 60 and 80 days of age. Frequency of distal airways Clara cells was maintained while mRNA levels for the mucin-encoding genes Muc5B and Muc5ac in lung homogenates increased 1.9 and 3.9 times at 60 days of infection (P. = 0.1609 and P. = 0.0001, respectively) and protein levels of the Clara cell marker CC10 decreased in the Pneumocystis-infected rats at 60 and 80 days of age (P. = 0.0118 & P. = 0.0388). CC10 and Muc5b co-localized in distal airway epithelium of Pneumocystis-infected rats at day 60. Co-localization of Muc5b and Ki67 as marker of mitosis in distal airways was not observed suggesting that Muc5b production by Clara cells was independent of mitosis. Notch levels remained similar and no transnucleation of activated Notch associated to Pneumocystis infection was detected. Unexpectedly, mucus was greatly increased at day 80 in Pneumocystis-infected rats receiving VPA suggesting that a Notch-independent mechanism was triggered. Overall, data suggests a Clara to goblet cell transdifferentiation mechanism induced by Pneumocystis and independent of Notch.
Lenguagedc.language.isoen
Publisherdc.publisherPublic Library of Science
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile
Link to Licensedc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
Sourcedc.sourcePLoS ONE
Keywordsdc.subjectBiochemistry, Genetics and Molecular Biology (all)
Keywordsdc.subjectAgricultural and Biological Sciences (all)
Títulodc.titlePrimary infection by Pneumocystis induces Notch-independent Clara cell mucin production in rat distal airways
Document typedc.typeArtículo de revista
dcterms.accessRightsdcterms.accessRightsAcceso Abierto
Catalogueruchile.catalogadorSCOPUS
Indexationuchile.indexArtículo de publicación SCOPUS
uchile.cosechauchile.cosechaSI


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Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Chile