AUTHOR=Wang Wei , Zhang Tie-Ning , Yang Ni , Wen Ri , Wang Yu-Jing , Zhang Bing-Lun , Yang Yu-Hang , Liu Chun-Feng 

TITLE=Transcriptome-wide identification of altered RNA m6A profiles in cardiac tissue of rats with LPS-induced myocardial injury

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1122317

DOI=10.3389/fimmu.2023.1122317

ISSN=1664-3224

ABSTRACT=<sec><title>Purpose</title><p>Myocardial injury is a common complication in patients with endotoxaemia/sepsis, especially in children. Moreover, it develops through an unclear pathophysiological mechanism, and effective therapies are lacking. Recently, RNA modification, particularly <italic>N</italic><sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification, has been found to be involved in various physiological processes and to play important roles in many diseases. However, the role of m<sup>6</sup>A modification in endotoxaemia/sepsis-induced myocardial injury is still in its infancy. Therefore, we attempted to construct the m<sup>6</sup>A modification map of myocardial injury in a rat model treated by lipopolysaccharide (LPS) and explore the role of m<sup>6</sup>A modification in LPS-induced myocardial injury.</p></sec><sec><title>Method</title><p>Myocardial injury adolescent rat model was constructed by intraperitoneal injection of LPS. m<sup>6</sup>A RNA Methylation Quantification Kit was used to detect overall level of m<sup>6</sup>A modification in rat cardiac tissue. m<sup>6</sup>A-specific methylated RNA immunoprecipitation followed by high-throughput sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were conducted to identify the altered m<sup>6</sup>A-modified genes and differentially expressed genes in cardiac tissue of rats treated by LPS and control rats (6 versus. 6). Bioinformatics was used to analyze the functions of differentially m<sup>6</sup>A modified genes, differentially expressed genes, and genes with both differential m<sup>6</sup>A modification and differential expression. qPCR was used to detect expression of m<sup>6</sup>A modification related enzymes.</p></sec><sec><title>Result</title><p>We found that the overall level of m<sup>6</sup>A modification in cardiac tissue of the LPS group was up-regulated compared with that of the control group. MeRIP-seq and RNA-seq results showed that genes with differential m<sup>6</sup>A modification, genes with differential expression and genes with both differential m<sup>6</sup>A modification and differential expression were closely associated with inflammatory responses and apoptosis. In addition, we found that m<sup>6</sup>A-related enzymes (Mettl16, Rbm15, Fto, Ythdc2 and Hnrnpg) were differentially expressed in the LPS group versus. the control group.</p></sec><sec><title>Conclusion</title><p>m<sup>6</sup>A modification is involved in the pathogenesis process of LPS-induced myocardial injury, possibly through the regulation of inflammatory response and apoptosis-related pathways. These results provide valuable information regarding the potential pathogenic mechanisms underlying LPS-induced myocardial injury.</p></sec>