Epigenetic alterations by DNA methylation in house dust mite-induced airway hyperresponsiveness

Yan Shang, Sandhya Das, Richard Rabold, James S.K. Sham, Wayne Mitzner, Wan Yee Tang

Research output: Contribution to journalArticle

Abstract

Asthma is one of the most prevalent chronic lung diseases, affecting 235 million individuals around the world, with its related morbidity and mortality increasing steadily over the last 20 years. Exposure to the environmental allergen, house dust mite (HDM), results in airway inflammation with a variable degree of airway obstruction. Although there has been much experimental work in the past using HDMchallenge models to understand mechanistic details in allergic inflammation and airway hyperresponsiveness (AHR), there has been no study on reprogramming of lung or airways mediated through epigenetic mechanisms in response to an acute HDM exposure. Malemice, 6 weeks of age,were administrated HDMextracts or saline at Days 1, 14, and 21. Exposure of mice to HDMextracts caused significant airway inflammation and increased AHR. These HDMchallenged mice also exhibited a change in global DNA methylation as compared with saline-exposed (control)mice. Next, by employing methylation-sensitive restriction fingerprinting,we identified a set of genes, showing aberrant methylation status, associated with the HDM-induced AHR. These candidate genes are known to be involved in cAMP signaling (pde4 d), Akt-signaling (akt1 s1), ion transport (tm6 sf1, pom121l2, and slc8a3), and fatty acid metabolism (acsl3). Slc8a3 and acsl3 were down-regulated, whereas pde4 d, akt1 s1, tm6 sf1, and pom121l2were up-regulated in themice exposed toHDM. Hence, our results suggest thatHDMexposure induces a series of aberrantmethylated genes that are potentially important for the development of allergic AHR.

Original languageEnglish (US)
Pages (from-to)279-287
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume49
Issue number2
DOIs
StatePublished - Aug 1 2013

Keywords

  • Airway hyperresponsiveness
  • DNA methylation
  • Epigenetics
  • House dust mite

ASJC Scopus subject areas

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

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