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A systematic approach to identify signalling pathways activated during short-term exposure to traffic-related urban air pollution from human blood

Vargas, José Eduardo
Kubesch, Nadine
Hernandéz-Ferrer, Carles
Carrasco-Turigas, Glória
Bustamante, Mariona
Nieuwenhuijsen, Mark
Gonzalez, Juan R.
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Abstract
The molecular mechanisms that promote pathologic alterations in human physiology mediated by short-term exposure to traffic pollutants remains not well understood. This work was to develop mechanistic networks to determine which specific pathways are activated by real-world exposures of traffic-related air pollution (TRAP) during rest and moderate physical activity (PA). A controlled crossover study to compare whole blood gene expression pre and post short-term exposure to high and low of TRAP was performed together with systems biology analysis. Twenty-eight healthy volunteers aged between 21 and 53 years were recruited. These subjects were exposed during 2 h to different pollution levels (high and low TRAP levels), while either cycling or resting. Global transcriptome profile of each condition was performed from human whole blood samples. Microarrays analysis was performed to obtain differential expressed genes (DEG) to be used as initial input for GeneMANIA software to obtain protein-protein (PPI) networks. Two networks were found reflecting high or low TRAP levels, which shared only 5.6 and 15.5% of its nodes, suggesting specific cell signaling pathways being activated in each environmental condition. However, gene ontology analysis of each PPI network suggests that each level of TRAP regulate common members of NF-κB signaling pathway. Our work provides the first approach describing mechanistic networks to understand TRAP effects on a system level.
Keywords
traffic-related air pollution, human interactome, systems biology, moderate physical activity
Date
2018
Type
Journal article
Journal
Environmental Science and Pollution Research
Book
Volume
25
Issue
29
Page Range
29572-29583
Article Number
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
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Open Access Status
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Controlled
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