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缺血再灌注损伤后小鼠心脏来源的细胞外囊泡中的长非编码 RNA 和 mRNAs 的改变。

Alterations of long noncoding RNAs and mRNAs in extracellular vesicles derived from the murine heart post-ischemia-reperfusion injury.

机构信息

Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

出版信息

J Cell Mol Med. 2022 Dec;26(24):6006-6018. doi: 10.1111/jcmm.17617. Epub 2022 Nov 28.

Abstract

Extracellular vesicles (EVs) play important roles in cardiovascular diseases by delivering their RNA cargos. However, the features and possible role of the lncRNAs and mRNAs in cardiac EVs during ischemia-reperfusion (IR) remain unclear. Therefore, we performed RNA sequencing analysis to profile the features of lncRNAs and mRNAs and predicted their potential functions. Here, we demonstrated that the severity of IR injury was significantly correlated with cardiac EV production. RNA sequencing identified 73 significantly differentially expressed (DE) lncRNAs (39 upregulated and 34 downregulated) and 720 DE-mRNAs (317 upregulated and 403 downregulated). Gene Ontology (GO) and pathway analysis were performed to predict the potential functions of the DE-lncRNAs and mRNAs. The lncRNA-miRNA-mRNA ceRNA network showed the possible functions of DE-lncRNAs with DE-mRNAs which are enriched in the pathways of T cell receptor signalling pathway and cell adhesion molecules. Moreover, the expressions of ENSMUST00000146010 and ENSMUST00000180630 were negatively correlated with the severity of IR injury. A significant positive correlation was revealed between TCONS_00010866 expression and the severity of the cardiac injury. These findings revealed the lncRNA and mRNA profiles in the heart derived EVs and provided potential targets and pathways involved in cardiac IR injury.

摘要

细胞外囊泡 (EVs) 通过传递其 RNA cargos 在心血管疾病中发挥重要作用。然而,在缺血再灌注 (IR) 期间心脏 EVs 中 lncRNAs 和 mRNAs 的特征和可能作用尚不清楚。因此,我们进行了 RNA 测序分析,以描绘 lncRNAs 和 mRNAs 的特征,并预测它们的潜在功能。在这里,我们证明了 IR 损伤的严重程度与心脏 EV 的产生显著相关。RNA 测序鉴定了 73 个显著差异表达 (DE) 的 lncRNAs (39 个上调和 34 个下调) 和 720 个 DE-mRNAs (317 个上调和 403 个下调)。进行了基因本体 (GO) 和通路分析,以预测 DE-lncRNAs 和 mRNAs 的潜在功能。lncRNA-miRNA-mRNA ceRNA 网络显示了 DE-lncRNAs 与 DE-mRNAs 的可能功能,这些基因富集在 T 细胞受体信号通路和细胞黏附分子途径中。此外,ENSMUST00000146010 和 ENSMUST00000180630 的表达与 IR 损伤的严重程度呈负相关。TCONS_00010866 的表达与心脏损伤的严重程度呈显著正相关。这些发现揭示了心脏衍生 EV 中的 lncRNA 和 mRNA 谱,并提供了涉及心脏 IR 损伤的潜在靶点和途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/969e/9753460/1207011c4071/JCMM-26-6006-g008.jpg

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