Formaldehyde-associated changes in micrornas: Tissue and temporal specificity in the rat nose, white blood cells, and bone marrow

Julia E. Rager, Benjamin Moeller, Sloane K. Miller, Dean Kracko, Melanie Doyle-Eisele, James A. Swenberg, Rebecca C. Fry

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) are critical regulators of gene expression, yet much remains unknown regarding their changes resulting from environmental exposures as they influence cellular signaling across various tissues. We set out to investigate miRNA responses to formaldehyde, a critical air pollutant and known carcinogen that disrupts miRNA expression profiles. Rats were exposed by inhalation to either 0 or 2 ppm formaldehyde for 7, 28, or 28 days followed by a 7-day recovery. Genome-wide miRNA expression profiles were assessed within the nasal respiratory epithelium, circulating white blood cells (WBC), and bone marrow (BM). miRNAs showed altered expression in the nose and WBC but not in the BM. Notably in the nose, miR-10b and members of the let-7 family, known nasopharyngeal carcinoma players, showed decreased expression. To integrate miRNA responses with transcriptional changes, genomewide messenger RNA profiles were assessed in the nose and WBC. Although formaldehyde-induced changes in miRNA and transcript expression were largely tissue specific, pathway analyses revealed an enrichment of immune system/inflammation signaling in the nose and WBC. Specific to the nose was enrichment for apoptosis/proliferation signaling, involving let-7a, let-7c, and let-7f. Across all tissues and time points assessed, miRNAs were predicted to regulate between 7% and 35% of the transcriptional responses and were suggested to play a role in signaling processes including immune/inflammation-related pathways. These data inform our current hypothesis that formaldehyde-induced inflammatory signals originating in the nose may drive WBC effects.

Original languageEnglish (US)
Article numberkft267
Pages (from-to)36-46
Number of pages11
JournalToxicological Sciences
Volume138
Issue number1
DOIs
StatePublished - Mar 1 2014
Externally publishedYes

Fingerprint

Organ Specificity
MicroRNAs
Nose
Formaldehyde
Rats
Bone
Leukocytes
Blood
Bone Marrow
Cells
Tissue
Cell signaling
Inflammation
Respiratory Mucosa
Air Pollutants
Nasal Mucosa
Immune system
Environmental Exposure
Regulator Genes
Gene expression

Keywords

  • Epigenetics
  • Formaldehyde
  • Gene expression
  • Inhalation
  • MicroRNA.

ASJC Scopus subject areas

  • Toxicology

Cite this

Formaldehyde-associated changes in micrornas : Tissue and temporal specificity in the rat nose, white blood cells, and bone marrow. / Rager, Julia E.; Moeller, Benjamin; Miller, Sloane K.; Kracko, Dean; Doyle-Eisele, Melanie; Swenberg, James A.; Fry, Rebecca C.

In: Toxicological Sciences, Vol. 138, No. 1, kft267, 01.03.2014, p. 36-46.

Research output: Contribution to journalArticle

Rager, Julia E. ; Moeller, Benjamin ; Miller, Sloane K. ; Kracko, Dean ; Doyle-Eisele, Melanie ; Swenberg, James A. ; Fry, Rebecca C. / Formaldehyde-associated changes in micrornas : Tissue and temporal specificity in the rat nose, white blood cells, and bone marrow. In: Toxicological Sciences. 2014 ; Vol. 138, No. 1. pp. 36-46.
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