RGD Reference Report - Epigenetic alterations by DNA methylation in house dust mite-induced airway hyperresponsiveness. - Rat Genome Database

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

Authors: Shang, Yan  Das, Sandhya  Rabold, Richard  Sham, James S K  Mitzner, Wayne  Tang, Wan-yee 
Citation: Shang Y, etal., Am J Respir Cell Mol Biol. 2013 Aug;49(2):279-87. doi: 10.1165/rcmb.2012-0403OC.
RGD ID: 13831300
Pubmed: PMID:23526225   (View Abstract at PubMed)
PMCID: PMC3824034   (View Article at PubMed Central)
DOI: DOI:10.1165/rcmb.2012-0403OC   (Journal Full-text)

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 HDM challenge 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. Male mice, 6 weeks of age, were administrated HDM extracts or saline at Days 1, 14, and 21. Exposure of mice to HDM extracts caused significant airway inflammation and increased AHR. These HDM-challenged 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 pom121l2 were up-regulated in the mice exposed to HDM. Hence, our results suggest that HDM exposure induces a series of aberrant methylated genes that are potentially important for the development of allergic AHR.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ACSL3HumanExperimental Allergic Asthma  ISOAcsl3 (Mus musculus) RGD 
Acsl3RatExperimental Allergic Asthma  ISOAcsl3 (Mus musculus) RGD 
Acsl3MouseExperimental Allergic Asthma  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Acsl3  (acyl-CoA synthetase long-chain family member 3)

Genes (Mus musculus)
Acsl3  (acyl-CoA synthetase long-chain family member 3)

Genes (Homo sapiens)
ACSL3  (acyl-CoA synthetase long chain family member 3)


Additional Information