Formaldehyde-induced changes in microRNA signaling [Agilent]

MicroRNAs (miRNAs) are critical regulators of gene expression, yet much remains unknown regarding miRNA changes resulting from environmental exposures and whether they influence pathway signaling across various tissues and time. To gain knowledge on these novel topics, we set out to investigate in vivo miRNA responses to inhaled formaldehyde, an important air pollutant known to disrupt miRNA expression profiles. Rats were exposed by inhalation to either 0 or 2 ppm formaldehyde (6 hours/day) for 7 days, 28 days, or 28 days followed by a 7 day recovery. Genome-wide miRNA expression profiles and associated signaling pathways were assessed within the nasal respiratory mucosa, circulating mononuclear white blood cells (WBC), and bone marrow (BM). Male Fischer rats received nose-only inhalation exposures of 2 ppm formaldehyde. Three exposure durations were investigated: (1) 2 ppm formaldehyde exposure, 6 hours/day, for 7 days (7-day group), (2) 2 ppm formaldehyde exposure, 6 hours/day, for 28 days (28-day group), and (3) 2 ppm formaldehyde exposure, 6 hours/day, for 28 days, with a 7 day recovery period following the last exposure (28-day plus recovery group). Control (unexposed) rats were placed in nose-only exposure tubes containing room air for the same duration. After the last exposure period (or the last recovery period for the 28-day plus recovery group), animals were euthanized. RNA were assessed from sampes collected from the nasal epithelium, circulating white blood cells, and bone marrow cells. Genome-wide miRNA expression profiles were evaluated using microarrays.

微小RNA（MicroRNAs，miRNAs）是基因表达的关键调控因子，然而目前对于环境暴露所诱导的miRNA表达变化，以及其能否在不同组织与时间维度上调控通路信号传导，仍有诸多未解之处。为探究上述全新研究方向，本研究旨在探究活体中miRNA对吸入甲醛的应答反应——甲醛是一种已知会干扰miRNA表达谱的重要空气污染物。实验大鼠通过吸入方式分别暴露于0 ppm或2 ppm甲醛环境中，每日暴露6小时，暴露时长分为7天、28天，以及28天暴露后辅以7天恢复期三种方案。研究人员对鼻呼吸道黏膜、循环单核白细胞（WBC）以及骨髓（BM）中的全基因组miRNA表达谱及相关信号通路进行了检测分析。本实验采用雄性费希尔（Fischer）大鼠，实施鼻吸入暴露方式，暴露浓度为2 ppm甲醛。本次研究共设置三种暴露时长方案：（1）每日6小时暴露于2 ppm甲醛环境，持续7天（7天暴露组）；（2）每日6小时暴露于2 ppm甲醛环境，持续28天（28天暴露组）；（3）每日6小时暴露于2 ppm甲醛环境，持续28天，末次暴露后设置7天恢复期（28天暴露+恢复期组）。对照组（未暴露）大鼠则置于仅通入室内空气的鼻暴露管中，暴露时长与对应实验组保持一致。在末次暴露期（或28天暴露+恢复期组的末次恢复期）结束后，对所有实验大鼠实施安乐死。研究人员对采集自鼻上皮、循环白细胞及骨髓细胞的样本中的核糖核酸（RNA）进行了检测分析。本次研究采用基因芯片（microarrays）对全基因组miRNA表达谱进行了评估。