Identification of Potential Novel Biomarkers and Signaling Pathways Related to Otitis Media Induced by Diesel Exhaust Particles Using Transcriptomic Analysis in an In Vivo System.
BACKGROUND
Air pollutants are associated with inflammatory diseases such as otitis media (OM). Significantly higher incidence rates of OM are reported in regions with air pollution. Diesel exhaust particles (DEPs) comprise a major class of contaminants among numerous air pollutants, and they are characterized by a carbonic mixture of polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs, and small amounts of sulfate, nitrate, metals and other trace elements. DEP exposure is a risk factor for inflammatory diseases. Our previous study identified potential biomarkers using gene expression microarray and pathway analyses in an in vitro system. Although in vitro investigations have been conducted to elucidate plausible biomarkers and molecular mechanisms related to DEP exposure, in vivo studies are necessary to identify the exact biological relevance regarding the incidence of OM caused by DEP exposure. In this study, we identified potential molecular biomarkers and pathways triggered by DEP exposure in a rodent model.


METHODS
Transcriptomic analysis was employed to identify novel potential biomarkers in the middle ear of DEP-exposed mice.


RESULTS
A total of 697 genes were differentially expressed in the DEP-exposed mice; 424 genes were upregulated and 273 downregulated. In addition, signaling pathways among the differentially expressed genes mediated by DEP exposure were predicted. Several key molecular biomarkers were identified including cholinergic receptor muscarinic 1 (CHRM1), erythropoietin (EPO), son of sevenless homolog 1 (SOS1), estrogen receptor 1 (ESR1), cluster of differentiation 4 (CD4) and interferon alpha-1 (IFNA1).


CONCLUSIONS
Our results shed light on the related cell processes and gene signaling pathways affected by DEP exposure. The identified biomarkers might be potential candidates for determining early diagnoses and effective treatment strategies for DEP-mediated disorders.
Department of Life Science, Dongguk University Biomedi Campus, 32, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-820, South Korea.|Institute of Environmental Medicine, Dongguk University, Seoul, South Korea.
Hyo Jeong
HJ
Kim
Department of Otorhinolaryngology-Head and Neck Surgery, Bundang CHA Medical Center, CHA University, Seongnam, South Korea.
So Young
SY
Kim
Department of Life Science, Dongguk University Biomedi Campus, 32, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-820, South Korea.|Institute of Environmental Medicine, Dongguk University, Seoul, South Korea.
Jee Young
JY
Kwon
Department of Life Science, Dongguk University Biomedi Campus, 32, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-820, South Korea.|Institute of Environmental Medicine, Dongguk University, Seoul, South Korea.
Yeo Jin
YJ
Kim
Department of Life Science, Dongguk University Biomedi Campus, 32, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-820, South Korea.|Institute of Environmental Medicine, Dongguk University, Seoul, South Korea.
Seung
S
Hun Kang
Department of Life Science, Dongguk University Biomedi Campus, 32, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-820, South Korea.|Institute of Environmental Medicine, Dongguk University, Seoul, South Korea.
Won-Hee
WH
Jang
Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, South Korea.
Jun Ho
JH
Lee
Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, South Korea.
Myung-Whan
MW
Seo
Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.
Jae-Jun
JJ
Song
Department of Life Science, Dongguk University Biomedi Campus, 32, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-820, South Korea.|Institute of Environmental Medicine, Dongguk University, Seoul, South Korea.
Young Rok
YR
Seo
Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, South Korea.
Moo Kyun
MK
Park
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D004432:Ear, Middle / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010033:Otitis Media / Q000175:diagnosis* / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome; D001335:Vehicle Emissions / Q000633:toxicity*
D015415:Biomarkers; D001335:Vehicle Emissions