Comprehensive analysis of transcriptome-wide m6A methylome in the lung tissues of mice with acute particulate matter
Juan Song1, Yingying Zeng1, Mengchan Zhu1
1Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200030, China.
Abstract:
Particulate matter (PM) exposure is identified as a critical risk factor for chronic airway diseases, but the biological mechanism of PM-induced lung damage was not fully elucidated. The m6A methylation, as the main member of epigenetic modifications, has been found to play an important role in different pulmonary diseases, but its regulatory effect on PM-induced lung damage remains unknown. This study firstly used the methylated RNA immunoprecipitation sequencing (MeRIP-seq) to reveal the m6A methylome profiles in the lung tissues of mice with acute PM exposure. Compared with the normal control, a total of 2210 differentially hypermethylated m6A peaks within 1879 genes and 1278 differentially hypomethylated m6A peaks within 1153 genes were identified in the PM-exposed group. Conjoint analysis of MeRIP-seq and high-throughput sequencing for RNA (RNA-seq) data predicated several potential pathways including MAPK signaling pathway, cell senescence, and cell cycle. Four m6A-modified differentially expressed genes (IL-1a, IL-1b, ADAM-8, and HMOX-1) were selected for validation using MeRIP-qPCR. Furthermore, the m6A-modified IL-1a promoted PM-induced inflammation via regulating MAPK signaling pathway. These results provide a new insight into the biological mechanism of PM-induced lung damage, and help us to develop new methods to prevent and treat PM-induced adverse health effects.
Insights
Particulate matter exposure damages lungs. This study reveals how m6A methylation, an epigenetic factor, alters gene expression in lung tissue, uncovering new mechanisms for PM-induced lung injury and potential treatments.
Area of Science:
- Environmental Health
- Epigenetics
- Pulmonary Medicine
Background:
- Particulate matter (PM) exposure is a key risk factor for chronic airway diseases.
- The precise biological mechanisms of PM-induced lung damage are not fully understood.
- The role of m6A methylation in PM-induced lung injury remains unexplored.
Purpose of the Study:
- To investigate the impact of acute PM exposure on the lung methylome using m6A sequencing.
- To identify differentially methylated genes and pathways involved in PM-induced lung damage.
- To elucidate the regulatory role of m6A methylation in PM-induced pulmonary inflammation.
Main Methods:
- Methylated RNA immunoprecipitation sequencing (MeRIP-seq) to profile the m6A methylome in mouse lung tissue after PM exposure.
- RNA sequencing (RNA-seq) to analyze gene expression changes.
- MeRIP-quantitative PCR (MeRIP-qPCR) for validation of specific m6A-modified genes.
Main Results:
- Significant alterations in m6A methylation patterns were observed in PM-exposed lungs, with 2210 hypermethylated and 1278 hypomethylated peaks identified.
- Conjoint analysis implicated pathways such as MAPK signaling, cell senescence, and cell cycle in PM-induced lung damage.
- The m6A-modified gene IL-1a was found to promote PM-induced inflammation by regulating the MAPK signaling pathway.
Conclusions:
- This study provides novel insights into the epigenetic mechanisms underlying PM-induced lung injury.
- m6A methylation plays a significant role in the response to particulate matter exposure in the lungs.
- Findings offer potential targets for developing new strategies to prevent and treat PM-related lung diseases.
