Exposure of airborne particulate matter (PM) with an aerodynamic diameter less than 2.5?μm (PM2.5) is epidemiologically associated with lung dysfunction and respiratory symptoms, including pulmonary fibrosis. However, whether epigenetic mechanisms are involved in PM2.5-induced pulmonary fibrosis is currently poorly understood. Herein, using a PM2.5-induced pulmonary fibrosis mouse model, we found that PM2.5 exposure leads to aberrant mRNA 5-methylcytosine (m5C) gain and loss in fibrotic lung tissues. Moreover, we showed the m5C-mediated regulatory map of gene functions in pulmonary fibrosis after PM2.5 exposure. Several genes act as m5C gain-upregulated factors, probably critical for the development of PM2.5-induced fibrosis in mouse lungs. These genes, including Lcn2, Mmp9, Chi3l1, Adipoq, Atp5j2, Atp5l, Atpif1, Ndufb6, Fgr, Slc11a1, and Tyrobp, are highly related to oxidative stress response, inflammatory responses, and immune system processes. Our study illustrates the first epitranscriptomic RNA m5C profile in PM2.5-induced pulmonary fibrosis and will be valuable in identifying biomarkers for PM2.5 exposure-related lung pathogenesis with translational potential.
PM2.5引起的肺纤维化鼠的表观转录组m5C图谱PM2.5是暴露在空气中动力学直径小于2.5μm微粒物质，其与肺功能障碍和呼吸道疾病相关，包括肺纤维化。但是，目前尚不清楚PM2.5诱导肺纤维化的表观遗传机制。在本文中，我们使用PM2.5诱导的肺纤维化小鼠模型，利用高通量测序技术及生物信息学分析方法发现PM2.5暴露导致纤维化肺组织mRNA 5-甲基胞嘧啶（m5C）位点数目及甲基化水平的异常变化。此外，分析结果展示了PM2.5暴露后m5C介导的肺纤维化基因功能的调控图谱。进一步筛选得到的m5C增益的上调基因，可能对PM2.5诱导的小鼠肺纤维化发展至关重要。这些基因包括Lcn2，Mmp9，Chi3l1，Adipoq，Atp5j2，Atp51，Atpif1，Ndufb6，Fgr，Slc11a1和Tyrobp，它们与氧化应激反应、炎症反应和免疫系统过程高度相关。我们的研究绘制了第一个PM2.5诱导的肺纤维化中RNA m5C图谱，对于开发PM2.5暴露相关性肺病的潜在生物标志物具有重要价值。





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