MicroRNA-mediated inflammation and coagulation effects in rats exposed to an inhaled analog of sulfur mustard.

摘要: Exposure of rats to 2-chloroethyl ethyl sulfide (CEES), an analog sulfur mustard, can cause acute lung injury (ALI), resulting in increased inflammation and coagulation altered levels plasma microRNAs (miRNAs). Rats were exposed aerosolized CEES euthanized 12 h later for collection tissue plasma. Profiling miRNAs plasma, using a TaqMan-based RT-PCR array, revealed 14 differentially expressed miRNAs. Target gene prediction pathway analysis miRNA-mediated regulation organismal injury, inflammation, respiratory diseases. miR-140-5p, marker ALI, was downregulated the lung, liver, kidney CEES-exposed rats, with concomitant increase expression markers IL-6 IL-1α factor (F3). rat airway epithelial cells (RL-65) (0.5 mM) caused cell death decrease miR-140-5p both media supernatant. This accompanied by cellular mRNA IL-6, IL-1α, F3, as well FGF9 EGR2, putative targets miR-140. Knockdown miR-140 specific oligos RL-65 mimicked vivo CEES-mediated effects, leading significantly FGF9, EGR2. Our study identifies mediator CEES-induced which could potentially be targeted therapy.