Circulating miRs-183-5p, -206-3p and -381-3p may serve as novel biomarkers for 4,4’-methylene diphenyl diisocyanate exposure

Background: Occupational exposure to the most widely used diisocyanate, 4,4’-methylene diphenyl diisocyanate (MDI), is a cause of occupational asthma (OA). Early recognition of MDI exposure and sensitization is essential for the prevention of MDI-OA. Objective: Identify circulating microRNAs (miRs) as novel biomarkers for early detection of MDI exposure and prevention of MDI-OA. Materials and methods: Female BALB/c mice were exposed to one of three exposure regimens: dermal exposure to 1% MDI in acetone; nose-only exposure to 4580 ± 1497 μg/m3 MDI-aerosol for 60 minutes; or MDI dermal exposure/sensitization followed by MDI-aerosol inhalation challenge. Blood was collected and miRCURY™ miRs qPCR Profiling Service was used to profile circulate miRs from dermally exposed mice. Candidate miRs were identified and verified from mice exposed to three MDI-exposure regimens by TaqMan® miR assays. Results: Up/down-regulation patterns of circulating mmu-miRs-183-5p, -206-3p and -381-3p were identified and verified. Circulating mmu-miR-183-5p was upregulated whereas mmu-miRs-206-3p and -381-3p were downregulated in mice exposed via all three MDI exposure regimens. Discussion and conclusion: Upregulation of circulating miR-183-5p along with downregulation of circulating miRs-206-3p and -381-3p may serve as putative biomarkers of MDI exposure and may be considered as potential candidates for validation in exposed human worker populations.

背景：对最广泛使用的二异氰酸酯——4,4'-甲撑二苯基二异氰酸酯（MDI）的职业暴露是职业性哮喘（OA）的成因。MDI暴露和致敏的早期识别对于预防MDI-OA至关重要。目标：识别循环miRNA（miRs）作为MDI暴露早期检测和预防MDI-OA的新型生物标志物。材料与方法：将雌性BALB/c小鼠暴露于三种暴露方案之一：1% MDI在丙酮中的皮肤暴露；仅鼻腔暴露于4580±1497 μg/m3 MDI气溶胶60分钟；或MDI皮肤暴露/致敏后进行MDI气溶胶吸入挑战。收集血液并使用miRCURY™ miRs qPCR分析服务对皮肤暴露小鼠的循环miRs进行检测。通过TaqMan® miR检测对暴露于三种MDI暴露方案的小鼠中识别并验证候选miRs。结果：确定了循环mmu-miRs-183-5p、-206-3p和-381-3p的上调/下调模式，并进行了验证。在所有三种MDI暴露方案中，循环mmu-miR-183-5p上调，而mmu-miRs-206-3p和-381-3p下调。讨论与结论：循环miR-183-5p的上调与循环miRs-206-3p和-381-3p的下调可能作为MDI暴露的潜在生物标志物，并可考虑作为验证暴露于人类工人群体中的潜在候选者。