Evaluating sex differences in miR‐106a expression in a mouse model of lung inflammation and asthma

Abstract

MicroRNAs (miRNAs) are oligonucleotides involved in various processes in the cell, including gene expression regulation. MicroRNA‐106a is involved in transcription regulation of the gene coding for interleukin 10 (IL‐10), an anti‐inflammatory cytokine, and has been implicated in asthma exacerbation in mice. However, despite the well‐known sex differences in human asthma incidence, no studies have been done evaluating sex differences on the impact of miR‐106a in asthma. In this study, we hypothesized that there are sex differences in miR‐106a expression in the lungs of asthmatic mice, under normal conditions and in response to air pollution challenge. To test this hypothesis, both male and female mice were exposed to house dust mites (HDM) or phosphate‐buffered saline (control) for 5 weeks to trigger the asthma phenotype. Mice were subsequently subjected to ozone challenge (2ppm, 3 hours) to model asthma exacerbations. The asthma phenotype was confirmed by lung histology, lung function testing using a rodent ventilator, and expression of inflammatory markers by Real Time PCR. To measure miRNA expression, lungs were harvested, total RNA was extracted and converted to cDNA. We performed Real Time PCR with specific primers for miR‐106a and the small RNA U6 (normalization control) using the miRCURY LNA® RT® kit. Our results show sex differences in expression of miR‐106a upon HDM and ozone challenge. Ozone exposure increased miR‐106a expression in non‐asthmatic females and asthmatic males when compared to filtered air exposed mice (p<0.0001 and p<0.05, respectively). Male asthmatic mice had higher miR‐106a expression than non‐asthmatic male mice (p<0.0001). However, the interaction between ozone exposure and sex was significant in non‐asthmatic mice only. We conclude that the observed differences in miR‐106a expression may be a result of different lung immune cells recruited to the male and female asthmatic lung. Understanding the mechanisms behind these sex differences may lead to future development of novel treatments for asthma.Support or Funding InformationThanks to the American Physiological Society Undergraduate Summer Research Fellowship for allowing me to do this research and to the NIH grants HL133520 and HL141618 for supporting this work.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.