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Transcriptomic profiling identifies a critical role of Nrf2 in regulating the inflammatory response to fly ash particles in mouse lung.

Abstract
Exposure to combustion-derived nanoparticles is recognized as a major health hazard, but the molecular responses are still insufficiently described. The transcription factor erythroid 2-related factor 2 (Nrf2, also known as NFE2L2) is a master regulator of the pulmonary defense system against insults by particulate matter. However, its downstream molecular processes are not fully characterized. In the current study, BALB/c wild-type (WT) and Nrf2-/- mice were exposed by intranasal administration to fly ash particles (F3-S; 20 mg/kg BW), which were collected from a municipal waste incinerator in China, for three consecutive days. Using a comparative transcriptomics approach, the pulmonary global gene expression profiles to F3-S exposure were characterized for both genotypes. The preponderance of the differentially-expressed genes (DEGs) in WT mice induced by the fly ash particles, was related to inflammation. Functional enrichment and molecular pathway mapping of the DEGs specific to Nrf2-/- mice exposed to the particles revealed that all of the top 10 perturbed molecular pathways were associated with the inflammatory response. Our study identified a transcriptional signature related to the initial pulmonary injury in mouse upon fly ash exposure, and suggests an anti-inflammatory role of Nrf2 in protecting the lung against such exposure.
AuthorsJingwen Zhang, Huiling Cui, Akhileshwar Namani, Jun Yao, Hong Deng, Xiuwen Tang, Xiu Jun Wang
JournalEcotoxicology and environmental safety (Ecotoxicol Environ Saf) Vol. 190 Pg. 110132 (Mar 01 2020) ISSN: 1090-2414 [Electronic] Netherlands
PMID31918253 (Publication Type: Journal Article)
CopyrightCopyright © 2019 Elsevier Inc. All rights reserved.
Chemical References
  • Coal Ash
  • NF-E2-Related Factor 2
  • Particulate Matter
  • Carbon
Topics
  • Animals
  • Carbon
  • China
  • Coal Ash (analysis)
  • Gene Expression Profiling
  • Incineration
  • Lung (chemistry)
  • Mice
  • Mice, Inbred BALB C
  • NF-E2-Related Factor 2 (metabolism)
  • Particulate Matter (toxicity)
  • Transcriptome

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