Exposure of airborne particulate matter (PM) with an aerodynamic diameter less than 2.5 μm (PM_2.5) is epidemiologically associated with lung dysfunction and respiratory symptoms, including pulmonary fibrosis. However, whether epigenetic mechanisms are involved in PM_2.5-induced pulmonary fibrosis is currently poorly understood. Herein, using a PM_2.5-induced pulmonary fibrosis mouse model, we found that PM_2.5 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 PM_2.5 exposure. Several genes act as m⁵C gain-upregulated factors, probably critical for the development of PM_2.5-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 PM_2.5-induced pulmonary fibrosis and will be valuable in identifying biomarkers for PM_2.5 exposure-related lung pathogenesis with translational potential.

流行病学上，暴露空气动力学直径小于 2.5 μm 的颗粒物 (PM _{2.5 ) 与肺功能障碍和呼吸道症状（包括}肺纤维化）相关。_{然而，目前对于 PM 2.5}诱导的肺纤维化是否涉及表观遗传机制尚不清楚。在此，使用 PM _2.5诱导的肺纤维化小鼠模型，我们发现PM _2.5暴露会导致纤维化肺组织中mRNA 5-甲基胞嘧啶 (m ^{5 C) 的异常增加和减少。}此外，我们还展示了PM _{2.5暴露后肺纤维化中 m} ⁵ C 介导的基因功能调控图。一些基因充当 m ⁵ C 增益上调因子，可能对 PM _2.5诱导的小鼠肺部纤维化的发展至关重要。这些基因包括Lcn2、Mmp9、Chi3l1、Adipoq、Atp5j2、Atp5l 、 Atpif1、Ndufb6、Fgr、Slc11a1和Tyrobp，与氧化应激反应、炎症反应和免疫系统过程高度相关。_{我们的研究阐明了 PM 2.5}诱导的肺纤维化中的第一个表观转录组 RNA m ⁵ C 谱，对于识别与 PM _2.5暴露相关的肺发病机制具有转化潜力的生物标志物具有重要价值。