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PLoS One. 2015 Jul 24;10(7):e0134057. doi: 10.1371/journal.pone.0134057. eCollection 2015.

Vitamin D Modulates Expression of the Airway Smooth Muscle Transcriptome in Fatal Asthma.

Author information

1
Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, United States of America.
2
Airways Biology Initiative, Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, Philadelphia, PA, United States of America.
3
Partners Personalized Medicine, Boston, MA, United States of America.
4
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America.
5
Partners Personalized Medicine, Boston, MA, United States of America; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America.

Abstract

Globally, 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.

PMID:
26207385
PMCID:
PMC4514847
DOI:
10.1371/journal.pone.0134057
[Indexed for MEDLINE]
Free PMC Article

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