Airway smooth muscle-specific transcriptomic signatures of glucocorticoid exposure

Mengyuan Kan, Cynthia Koziol-White, Maya Shumyatcher, Martin Johnson, William Jester, Reynold A. Panettieri, Blanca E. Himes

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Glucocorticoids, commonly used asthma controller medications, decrease symptoms in most patients, but some remain symptomatic despite high-dose treatment. The physiological basis underlying the glucocorticoid response, especially in asthma patients with severe, refractory disease, is not fully understood. We sought to identify differences between the transcriptomic response of airway smooth muscle (ASM) cells derived from donors with fatal asthma and donors without asthma to glucocorticoid exposure and to compare ASM-specific changes with those observed in other cell types. In cells derived from nine donors with fatal asthma and eight donors without asthma, RNA sequencing was used to measure ASM transcriptome changes after exposure to budesonide (100 nM 24 h) or control vehicle (DMSO). Differential expression results were obtained for this dataset, as well as 13 publicly available glucocorticoid-response transcriptomic datasets corresponding to seven cell types. Specific genes were differentially expressed in response to glucocorticoid exposure (7,835 and 6,957 in ASM cells derived from donors with fatal asthma and donors without asthma, respectively; adjusted P value, 0.05). Transcriptomic changes in response to glucocorticoid exposure were similar in ASM derived from donors with fatal asthma and donors without asthma, with enriched ontological pathways that included cytokine- and chemokine-related categories. A comparison of glucocorticoid-induced changes in the nonasthma ASM transcriptome with those observed in six other cell types showed that ASM has a distinct glucocorticoid-response signature that is also present in ASM cells from donors with fatal asthma.

Original languageEnglish (US)
Pages (from-to)110-120
Number of pages11
JournalAmerican journal of respiratory cell and molecular biology
Volume61
Issue number1
DOIs
StatePublished - Jan 1 2019

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Keywords

  • Airway smooth muscle
  • Asthma
  • Glucocorticoid response
  • Integration
  • RNA-Seq

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