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.

Hyo Jeong Kim,Jae-Jun Song,So Young Kim,Won-Hee Jang,Moo Kyun Park,Jun Ho Lee,Young Rok Seo,Seung Hun Kang,Yeo Jin Kim,Jee Young Kwon,Myung-Whan Seo

doi:10.1371/journal.pone.0166044

Abstract

IntroductionAir 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.MethodsTranscriptomic analysis was employed to identify novel potential biomarkers in the middle ear of DEP-exposed mice.ResultsA 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).ConclusionsOur 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.

Highlights

Air pollutants are associated with inflammatory diseases such as otitis media (OM)
Our results shed light on the related cell processes and gene signaling pathways affected by Diesel exhaust particles (DEPs) exposure
Several technological advances have alleviated nitrogen oxide emission and reduced the particulate mass produced by diesel engines, such engines still produce high levels of DEPs compared with gasoline engines

Summary

Introduction

Air pollutants are associated with inflammatory diseases such as otitis media (OM). 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. 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. We identified potential molecular biomarkers and pathways triggered by DEP exposure in a rodent model

Methods

Discussion

Conclusion