Loss of exosomal LncRNA HCG15 prevents acute myocardial ischemic injury through the NF-κB/p65 and p38 pathways.
Loss of exosomal LncRNA HCG15 prevents acute myocardial ischemic injury through the NF-κB/p65 and p38 pathways.
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DOI：
10.1038/s41419-021-04281-8
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发表时间：
2021-10-27
影响因子：
9
通讯作者：
Jiang X
中科院分区：
文献类型：
--
作者：
Lin B;Chen X;Lu C;Xu J;Qiu Y;Liu X;Song H;Chen A;Xiong J;Wang K;Yuan Y;Shi L;Zhong L;Jiang X
外来体是纳米尺寸的双层膜囊泡，其可以通过转运生物活性分子（包括非编码RNA、mRNA和蛋白质）来介导细胞间通信。研究表明，外泌体在急性心肌梗死（AMI）中发挥重要作用，但外泌体长非编码RNA（lncRNA）在AMI中的作用及调控尚不清楚。因此，进行RNA测序（RNA-Seq）以研究来自MI患者的外来体lncRNA转录组，并鉴定了MI组和对照组之间的65个差异表达的lncRNA。qRT-PCR结果显示，差异表达的lncRNA中HCG 15与cTnT的相关性最高，受试者工作特征（ROC）分析显示，HCG 15对AMI的诊断有一定的帮助。HCG 15表达上调促进心肌细胞凋亡和炎性细胞因子的产生，并抑制细胞增殖。我们还证实，缺氧条件下AC 16心肌细胞中HCG 15主要包裹在exosomes中，通过激活NF-κB/p65和p38通路，促进心肌细胞凋亡，释放炎性因子，抑制细胞增殖，而抑制HCG 15的表达则产生相反的作用。HCG 15过表达加重C57 BL/6 J小鼠心脏IR损伤。这项研究不仅有助于阐明外泌体lncRNA在AMI发病机制中的作用，而且有助于开发新的治疗策略。
Exosomes are nanosized bilayer membrane vesicles that may mediate intercellular communication by transporting bioactive molecules, including noncoding RNAs, mRNAs, and proteins. Research has shown that exosomes play an important role in acute myocardial infarction (AMI), but the function and regulation of exosomal long noncoding RNAs (lncRNAs) in AMI are unclear. Thus, RNA sequencing (RNA-Seq) was conducted to investigate the exosomal lncRNA transcriptome from MI patients and identified 65 differentially expressed lncRNAs between the MI and control groups. HCG15, one of the differentially expressed lncRNAs, was verified to have the highest correlation with cTnT by qRT-PCR, and it also contributed to the diagnosis of AMI by receiver operating characteristic (ROC) analysis. Upregulation of HCG15 expression facilitated cardiomyocyte apoptosis and inflammatory cytokine production and inhibited cell proliferation. We also confirmed that HCG15 was mainly wrapped in exosomes from AC16 cardiomyocytes under hypoxia, which contributed to cardiomyocyte apoptosis, the release of inflammatory factors, and inhibition of cell proliferation via the activation of the NF-κB/p65 and p38 pathways, whereas suppressing the expression of HCG15exerted opposite effects, In addition, Overexpression of HCG15 aggravated cardiac IR injury in C57BL/6J mice. This study not only helps elucidate exosomal lncRNA function in AMI pathogenesis but also contributes to the development of novel therapeutic strategies.
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影响因子：
7.7
作者：
Wang, Xiaohong;Gu, Haitao;Fan, Guo-Chang
通讯作者：
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影响因子：
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作者：
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Tong W
DOI：
10.1016/j.bbrc.2018.08.113
发表时间：
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影响因子：
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作者：
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