4.7 Article

Identification of long non-coding RNA and circular RNA in mice after intra-tracheal instillation with fine particulate matter

Journal

CHEMOSPHERE
Volume 235, Issue -, Pages 519-526

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.chemosphere.2019.06.122

Keywords

PM2.5; Inflammation; NLRP3 inflammasome; Long non-coding RNA; Circular RNA

Funding

  1. Beijing Municipal Natural Science Foundation [7161013, 7174357]
  2. Capital Foundation of Medical Development
  3. National Key Research and Development Plan [2017YFC1309500]

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Background: Fine particulate matter (PM2.5) exposure has been proved to be associated with respiratory diseases in epidemiological studies, but the underlying mechanisms are not clear. One of the most important mechanisms involved is inflammation. Non-coding RNAs are proposed to play crucial roles in epigenetic modulation and post-transcriptional regulation. Identification of non-coding RNAs can show us the new insight into the molecular toxicity of PM2.5. Materials and methods: antra-tracheal instillation of saline or PM2.5 was performed in BALB/c Mice once a week for consecutive eight weeks. Genomewide transcriptome profiling of coding genes, long non coding RNAs (IncRNAs), and circular RNAs (circRNAs) in mice lung were done by ribosomal RNA depleted RNA sequencing. Lung histological alternations were observed in haematoxylin and eosin (HE) staining sections. The expressions of pro-inflammatory cytokines and Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome were quantified by qRT-PCR, ELISA and Western blot. Results: 1873 coding genes, 885 IncRNAs and 142 circRNAs were differentially expressed in lung tissues of the saline and PM2.5 exposed mice. The upregulated expressions of IncRNA NONMMUT065867, IncRNA NONMMUT064312, IncRNA NONMMUT018123 and the downregulated expressions of circRNA CBT15_circR_1011, circRNA mm9_circ_005915 were identified by qRT-PCR in PM2.5 group. The pulmonary inflammation score was higher in PM2.5 group. What's more, the expressions of pro-inflammatory cytokines and NLRP3 inflammasome were upregulated in PM2.5 exposed mice. Conclusion: PM2.5 causes lung inflammation and increases the expression of NLRP3 inflammasome. The identified novel IncRNAs and circRNAs may paly important role in the development of lung inflammation caused by PM2.5. (C) 2019 Published by Elsevier Ltd.

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