Epitranscriptomic 5-Methylcytosine Profile in PM2.5-induced Mouse Pulmonary Fibrosis

Xiao Han; Hanchen Liu; Zezhong Zhang; Wenlan Yang; Chunyan Wu; Xueying Liu; Fang Zhang; Baofa Sun; Yongliang Zhao; Guibin Jiang; Yun-Gui Yang; Wenjun Ding

doi:10.1016/j.gpb.2019.11.005

Epitranscriptomic 5-Methylcytosine Profile in PM_2.5-induced Mouse Pulmonary Fibrosis

Genomics Proteomics Bioinformatics. 2020 Feb;18(1):41-51. doi: 10.1016/j.gpb.2019.11.005. Epub 2020 Mar 3.

Authors

Xiao Han¹, Hanchen Liu², Zezhong Zhang³, Wenlan Yang⁴, Chunyan Wu³, Xueying Liu², Fang Zhang², Baofa Sun⁵, Yongliang Zhao⁵, Guibin Jiang⁶, Yun-Gui Yang⁷, Wenjun Ding⁸

Affiliations

¹ College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China.
² College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
³ College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China.
⁴ CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China.
⁵ CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
⁶ Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
⁷ CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China; Institute of Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: ygyang@big.ac.cn.
⁸ College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China. Electronic address: dingwj@ucas.ac.cn.

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.

Keywords: Immune response; Inflammation; PM(2.5) exposure; Pulmonary fibrosis; mRNA m(5)C.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

5-Methylcytosine / metabolism*
Animals
Biomarkers / metabolism
Disease Models, Animal
Male
Mice
Mice, Inbred C57BL
Oxidative Stress
Particulate Matter / toxicity*
Pulmonary Fibrosis / chemically induced*
Pulmonary Fibrosis / metabolism*
Pulmonary Fibrosis / pathology

Substances

Biomarkers
Particulate Matter
5-Methylcytosine