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dc.contributor.authorHimes, Blanca E.en_US
dc.contributor.authorKoziol-White, Cynthiaen_US
dc.contributor.authorJohnson, Martinen_US
dc.contributor.authorNikolos, Christinaen_US
dc.contributor.authorJester, Williamen_US
dc.contributor.authorKlanderman, Barbaraen_US
dc.contributor.authorLitonjua, Augusto A.en_US
dc.contributor.authorTantisira, Kelan G.en_US
dc.contributor.authorTruskowski, Kevinen_US
dc.contributor.authorMacDonald, Kevinen_US
dc.contributor.authorPanettieri, Reynold A.en_US
dc.contributor.authorWeiss, Scott T.en_US
dc.date.accessioned2015-08-03T13:59:26Z
dc.date.issued2015en_US
dc.identifier.citationHimes, B. E., C. Koziol-White, M. Johnson, C. Nikolos, W. Jester, B. Klanderman, A. A. Litonjua, et al. 2015. “Vitamin D Modulates Expression of the Airway Smooth Muscle Transcriptome in Fatal Asthma.” PLoS ONE 10 (7): e0134057. doi:10.1371/journal.pone.0134057. http://dx.doi.org/10.1371/journal.pone.0134057.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:17820667
dc.description.abstractGlobally, asthma is a chronic inflammatory respiratory disease affecting over 300 million people. Some asthma patients remain poorly controlled by conventional therapies and experience more life-threatening exacerbations. Vitamin D, as an adjunct therapy, may improve disease control in severe asthma patients since vitamin D enhances glucocorticoid responsiveness and mitigates airway smooth muscle (ASM) hyperplasia. We sought to characterize differences in transcriptome responsiveness to vitamin D between fatal asthma- and non-asthma-derived ASM by using RNA-Seq to measure ASM transcript expression in five donors with fatal asthma and ten non-asthma-derived donors at baseline and with vitamin D treatment. Based on a Benjamini-Hochberg corrected p-value <0.05, 838 genes were differentially expressed in fatal asthma vs. non-asthma-derived ASM at baseline, and vitamin D treatment compared to baseline conditions induced differential expression of 711 and 867 genes in fatal asthma- and non-asthma-derived ASM, respectively. Functional gene categories that were highly represented in all groups included extracellular matrix, and responses to steroid hormone stimuli and wounding. Genes differentially expressed by vitamin D also included cytokine and chemokine activity categories. Follow-up qPCR and individual analyte ELISA experiments were conducted for four cytokines (i.e. CCL2, CCL13, CXCL12, IL8) to measure TNFα-induced changes by asthma status and vitamin D treatment. Vitamin D inhibited TNFα-induced IL8 protein secretion levels to a comparable degree in fatal asthma- and non-asthma-derived ASM even though IL8 had significantly higher baseline levels in fatal asthma-derived ASM. Our findings identify vitamin D-specific gene targets and provide transcriptomic data to explore differences in the ASM of fatal asthma- and non-asthma-derived donors.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0134057en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514847/pdf/en
dash.licenseLAAen_US
dc.titleVitamin D Modulates Expression of the Airway Smooth Muscle Transcriptome in Fatal Asthmaen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorLitonjua, Augusto A.en_US
dc.date.available2015-08-03T13:59:26Z
dc.identifier.doi10.1371/journal.pone.0134057*
dash.authorsorderedfalse
dash.contributor.affiliatedLitonjua, Augusto A.
dash.contributor.affiliatedTantisira, Kelan
dash.contributor.affiliatedWeiss, Scott


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