Tolerance to nitroglycerin(GTN)greatly limits its long-time application,and the underlying mechanism remains largely unexplored.In the present study,we aimed to investigate the comprehensive changes in the transcripto...Tolerance to nitroglycerin(GTN)greatly limits its long-time application,and the underlying mechanism remains largely unexplored.In the present study,we aimed to investigate the comprehensive changes in the transcriptome of rat aorta tolerant to GTN by analyzing lncRNA expression.We employed the RNA sequencing(RNA-seq)technique to identify mRNAs and lncRNAs.Ingenuity pathway analysis(IPA)was used for pathway and functional analysis.RT-qPCR was used to validate the RNA-seq results.We identified 22788 genes(reads per kilobase million[RPKM]>0.1,14720 protein-coding genes and 4408 lncRNAs),including 115 differentially expressed(DE)mRNAs(65 up-regulated and 50 down-regulated)and 104 DE lncRNAs(56 up-regulated and 48 down-regulated),in GTN-tolerant aortas.IPA revealed the inhibition of a canonical pathway“Signaling by Rho Family GTPases”and alteration in six upstream regulators.Functional analysis showed that 11 genes were related to“disorder of blood pressure”.We predicted the cis-target genes of DE lncRNAs by the analysis of their neighboring genes.The results revealed the 28 DE lncRNAs adjacent to the 26 protein-coding genes.Many DE mRNAs and cis-target genes of DE lncRNAs have been implicated in the regulation of blood pressure or cell contraction.These results suggested that the dysregulated mRNAs and lncRNAs contributed to the development of GTN tolerance and could serve as potential targets to prevent and reverse GTN tolerance.展开更多
基金Scientific Research Fund of Hunan Provincial Education Department(Grant No.17B188,18A490)。
文摘Tolerance to nitroglycerin(GTN)greatly limits its long-time application,and the underlying mechanism remains largely unexplored.In the present study,we aimed to investigate the comprehensive changes in the transcriptome of rat aorta tolerant to GTN by analyzing lncRNA expression.We employed the RNA sequencing(RNA-seq)technique to identify mRNAs and lncRNAs.Ingenuity pathway analysis(IPA)was used for pathway and functional analysis.RT-qPCR was used to validate the RNA-seq results.We identified 22788 genes(reads per kilobase million[RPKM]>0.1,14720 protein-coding genes and 4408 lncRNAs),including 115 differentially expressed(DE)mRNAs(65 up-regulated and 50 down-regulated)and 104 DE lncRNAs(56 up-regulated and 48 down-regulated),in GTN-tolerant aortas.IPA revealed the inhibition of a canonical pathway“Signaling by Rho Family GTPases”and alteration in six upstream regulators.Functional analysis showed that 11 genes were related to“disorder of blood pressure”.We predicted the cis-target genes of DE lncRNAs by the analysis of their neighboring genes.The results revealed the 28 DE lncRNAs adjacent to the 26 protein-coding genes.Many DE mRNAs and cis-target genes of DE lncRNAs have been implicated in the regulation of blood pressure or cell contraction.These results suggested that the dysregulated mRNAs and lncRNAs contributed to the development of GTN tolerance and could serve as potential targets to prevent and reverse GTN tolerance.
