Epitranscriptomic 5-Methylcytosine Profile in PM<b>2.5</b>-Induced Mouse Pulmonary Fibrosis

Abstract

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.