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Culturing of Human Nasal Epithelial Cells at the Air Liquid Interface

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Published on: October 8, 2013

Formaldehyde and epigenetic alterations: microRNA changes in the nasal epithelium of nonhuman primates

Julia E Rager¹, Benjamin C Moeller, Melanie Doyle-Eisele

¹Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

Environmental Health Perspectives

|January 17, 2013

Abstract

Background:

Formaldehyde is an air pollutant present in both indoor and outdoor atmospheres. Because of its ubiquitous nature, it is imperative to understand the mechanisms underlying formaldehyde-induced toxicity and carcinogenicity. MicroRNAs (miRNAs) can influence disease caused by environmental exposures, yet miRNAs are understudied in relation to formaldehyde. Our previous investigation demonstrated that formaldehyde exposure in human lung cells caused disruptions in miRNA expression profiles in vitro.

Objectives:

Using an in vivo model, we set out to test the hypothesis that formaldehyde inhalation exposure significantly alters miRNA expression profiles within the nasal epithelium of nonhuman primates.

Methods:

Cynomolgus macaques were exposed by inhalation to approximately 0, 2, or 6 ppm formaldehyde for 6 hr/day for 2 consecutive days. Small RNAs were extracted from nasal samples and assessed for genome-wide miRNA expression levels. Transcriptional targets of formaldehyde-altered miRNAs were computationally predicted, analyzed at the systems level, and assessed using real-time reverse transcriptase polymerase chain reaction (RT-PCR).

Results:

Expression analysis revealed that 3 and 13 miRNAs were dysregulated in response to 2 and 6 ppm formaldehyde, respectively. Transcriptional targets of the miRNA with the greatest increase (miR-125b) and decrease (miR-142-3p) in expression were predicted and analyzed at the systems level. Enrichment was identified for miR-125b targeting genes involved in apoptosis signaling. The apoptosis-related targets were functionally tested using RT-PCR, where all targets showed decreased expression in formaldehyde-exposed samples.

Conclusions:

Formaldehyde exposure significantly disrupts miRNA expression profiles within the nasal epithelium, and these alterations likely influence apoptosis signaling.

Insights

Formaldehyde inhalation alters microRNA (miRNA) expression in primate nasal tissue, impacting genes involved in apoptosis signaling. This study reveals potential mechanisms of formaldehyde toxicity and carcinogenicity.

Area of Science:

Environmental Health
Molecular Biology
Toxicology

Background:

Formaldehyde is a common air pollutant linked to toxicity and carcinogenicity.
MicroRNAs (miRNAs) play a role in environmental exposure-related diseases but are understudied concerning formaldehyde.
Previous in vitro studies showed formaldehyde disrupts miRNA expression in human lung cells.

Purpose of the Study:

To investigate the in vivo effects of formaldehyde inhalation on miRNA expression profiles.
To test the hypothesis that formaldehyde exposure alters miRNA expression in the nasal epithelium of nonhuman primates.

Main Methods:

Cynomolgus macaques were exposed to varying concentrations of formaldehyde via inhalation.
Genome-wide miRNA expression levels were analyzed from nasal tissue samples.
Computational prediction and RT-PCR were used to assess miRNA targets and their function.

Main Results:

Formaldehyde inhalation dysregulated specific miRNAs in a dose-dependent manner (3 miRNAs at 2 ppm, 13 miRNAs at 6 ppm).
Key miRNAs, miR-125b and miR-142-3p, showed altered expression.
Predicted targets of miR-125b involved in apoptosis signaling showed decreased expression upon formaldehyde exposure.

Conclusions:

Formaldehyde inhalation significantly disrupts miRNA expression profiles in the nasal epithelium.
These miRNA alterations are likely involved in modulating apoptosis signaling pathways, contributing to formaldehyde-induced toxicity.

Read full analysis

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