Integrative Analysis of m⁶A Methylation and Transcriptomic Profiles in Cortical Tissues of Mice with Sepsis-Associated Encephalopathy.
6 affiliations
- 1Maternal and Child Healthcare Medical Research Institute, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, People's Republic of China.
- 2Hengyang Medical School, University of South China, Hengyang, People's Republic of China.
- 3Department of Critical Care Medicine, Shenzhen Third People's Hospital, Shenzhen, People's Republic of China.
- 4Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, People's Republic of China.
- 5Department of Anesthesiology, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, People's Republic of China.
- 6Shenzhen Key Laboratory of Maternal and Child Health and Diseases, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, People's Republic of China.
Abstract
Background
Sepsis-associated encephalopathy (SAE) is a common and severe complication in septic patients, characterized by the increased mortality and cognition dysfunction. N6-Methyladenosine (m⁶A), one of the most prevalent RNA modifications, plays crucial roles in the central nervous system by regulating RNA metabolism. However, its involvement in the pathogenesis of SAE remains unexplored.Methods
RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation (MeRIP)-sequencing were performed to analyze the transcriptomic profiles and m⁶A methylation in the brain cortex of LPS-induced septic mice. Bioinformatics analysis was carried out to identify genes with altered m⁶A methylation and differential expression. Target genes and m⁶A regulators were further validated using quantitative reverse transcription polymerase chain reaction (RT-qPCR).Results
Numerous genes exhibited differential expression and m⁶A modification in the cortical tissues of septic mice. Gene function enrichment analysis revealed that genes with differential expression were enriched in pathways related to immune and inflammatory responses as well as neuroactive ligand-receptor interaction, and genes with differential m⁶A modification showed significant associations with pathways related to neurodegeneration, synapse function and metabolism. Comprehensive analysis of genes with both altered m⁶A methylation and transcription identified several key genes highly associated with inflammatory processes. Validation experiments confirmed significant dysregulation of mRNA levels for several target genes (Ahsg, Alb, Apoa1, Serpina1b, Serpinf2, and Serpina3K) and m⁶A regulators (Mettl3, Mettl16, Igfbp1 and Igfbp3) in the cortex of septic mice.Conclusion
This study provided a transcriptome-wide analysis of m⁶A methylation in the cortical tissues of septic mice, suggesting that m⁶A-mediated regulation of inflammatory gene expression is associated with the pathogenesis of SAE. The findings presented valuable insights into the mechanisms of sepsis-associated brain injury and potential therapeutic targets.
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BibTeX
@article{zhao2026integrative,
title = {{Integrative Analysis of m⁶A Methylation and Transcriptomic Profiles in Cortical Tissues of Mice with Sepsis-Associated Encephalopathy.}},
author = {Juan Zhao and Tengfei Zhu and Chao Zhao and Xu Huang and Fang Yao and Yueyuan Qin and Baojiang Wang and Gehui Li and Shan Duan},
journal = {Journal of inflammation research},
year = {2026},
month = oct,
doi = {10.2147/jir.s586027},
url = {https://europepmc.org/article/MED/42936262},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Integrative Analysis of m⁶A Methylation and Transcriptomic Profiles in Cortical Tissues of Mice with Sepsis-Associated Encephalopathy.
AU - Juan Zhao
AU - Tengfei Zhu
AU - Chao Zhao
AU - Xu Huang
AU - Fang Yao
AU - Yueyuan Qin
AU - Baojiang Wang
AU - Gehui Li
AU - Shan Duan
PY - 2026
DA - 2026/10/22
JO - Journal of inflammation research
DO - 10.2147/jir.s586027
UR - https://europepmc.org/article/MED/42936262
AB - Background Sepsis-associated encephalopathy (SAE) is a common and severe complication in septic patients, characterized by the increased mortality and cognition dysfunction. N6-Methyladenosine (m⁶A), one of the most prevalent RNA modifications, plays crucial roles in the central nervous system by regulating RNA metabolism. However, its involvement in the pathogenesis of SAE remains unexplored.Methods RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation (MeRIP)-sequencing were performed to analyze the transcriptomic profiles and m⁶A methylation in the brain cortex of LPS-induced septic mice. Bioinformatics analysis was carried out to identify genes with altered m⁶A methylation and differential expression. Target genes and m⁶A regulators were further validated using quantitative reverse transcription polymerase chain reaction (RT-qPCR).Results Numerous genes exhibited differential expression and m⁶A modification in the cortical tissues of septic mice. Gene function enrichment analysis revealed that genes with differential expression were enriched in pathways related to immune and inflammatory responses as well as neuroactive ligand-receptor interaction, and genes with differential m⁶A modification showed significant associations with pathways related to neurodegeneration, synapse function and metabolism. Comprehensive analysis of genes with both altered m⁶A methylation and transcription identified several key genes highly associated with inflammatory processes. Validation experiments confirmed significant dysregulation of mRNA levels for several target genes (Ahsg, Alb, Apoa1, Serpina1b, Serpinf2, and Serpina3K) and m⁶A regulators (Mettl3, Mettl16, Igfbp1 and Igfbp3) in the cortex of septic mice.Conclusion This study provided a transcriptome-wide analysis of m⁶A methylation in the cortical tissues of septic mice, suggesting that m⁶A-mediated regulation of inflammatory gene expression is associated with the pathogenesis of SAE. The findings presented valuable insights into the mechanisms of sepsis-associated brain injury and potential therapeutic targets.
SN - 1178-7031
ER -