Comprehensive bioinformatic analysis identified m6A methylation as an important regulator in mediating immune response during idiopathic pulmonary arterial hypertension

Abstract BackgroundDespite its functional importance in various fundamental bioprocesses, studies of N6-methyladenosine (m 6 A) in the pulmonary arterial hypertension (PAH) are lacking. Here we studied the potential relevance of m 6 A RNA methylation and immune response in PAH development.MethodsWe constructed a monocrotaline (MCT) induced PAH rat model and performed Methylated RNA immunoprecipitation sequencing (MeRIP-Seq). The 18 idiopathic PAH (IPAH) microarray data obtained from the GEO database was used to construct co-expression networks by weighted gene co-expression network analysis (WGCNA). CIBERSORT was used to investigate the effect of m 6 A methylation on immune cell infiltration during PAH.ResultsA differential pattern of m 6 A abundance, mainly up-methylation, was observed in the lung tissues of rats with MCT induced PAH. By WGCNA, multi-list pathway enrichment analysis and protein-protein interaction (PPI) analysis, we found that m 6 A methylation modification may play important roles in mediating immune response during PAH. CYBERSORT algorithm indicated that the m 6 A methylation can drive monocyte to form M1 macrophage, which may be mediated by CCR5 and CXCL9.ConclusionCollectively, m 6 A landscape is altered in PAH. We summarize newly discovered m 6 A in controlling immune response, which caused activation of M1 macrophage during PAH. It’s provided a novel insight into the therapeutic mechanisms of PAH.