Epitranscriptomic 5-Methylcytosine Profile in PM(2.5)-induced Mouse Pulmonary Fibrosis

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 (m(5)C) gain and loss in fibrotic lung tissues. Moreover, we showed the m(5)C-mediated regulatory map of gene functions in pulmonary fibrosis after PM(2.5) exposure. Several genes act as m(5)C 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 m(5)C 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.