急性冠状动脉综合征患者树突状细胞衍生的 lncRNA。

Zhenglong Wang, K. E. Changhao, Yuheng Chen, Yongchao Zhao, Yuanjie He, Xiao Liang, Qingxian Tu, Min Xu, Fujia Guo, Junbo Ge, Bei Shi
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摘要

长非编码 RNA(lncRNA)和树突状细胞(DC)在急性冠状动脉综合征(ACS)的发病中起着至关重要的作用;然而,其机制仍不清楚。为了研究这个问题,我们分析了急性冠状动脉综合征患者单核细胞衍生的树突状细胞(DC)中不同表达的lncRNAs。外周血单核细胞被转化为 moDCs。利用电子显微镜(EM)和流式细胞术(FCM)分别分析了细胞形态和moDC特异性标记物(CD80、CD86、CD11c、CD14和HLA-DR)的表达水平。利用基因测序、基因本体论和京都基因和基因组百科全书预测了差异表达的 lncRNA 及其功能。通过过表达或沉默候选lncRNA,分析了标志物、信号通路分子(p-PI3K和p-AKT)、炎症细胞因子(IL-6和IL-12p70)和靶基因(C-C motif趋化因子配体(CCL)15和CCL14)的表达水平。EM显示细胞悬浮在树突状伪足中。CD11c和HLA-DR上调,而CD80和CD86下调。UA组与ST组的比较显示,差异表达的lncRNA数量最多(n = 113),其次是UA组与NST组(n = 115)、CON组与NST组(n = 49)和CON组与ST组(n = 35);然而,CON组与UA组和ST组与NST组的数量较少。慢病毒过表达智能沉默子-CCL15-CCL14 后,moDC 特异性标记物表达、信号通路分子、炎症细胞因子和 CCL14 均上调;但转染 siRNA 后,表达水平下降。moDCs的形态、功能和lncRNA表达因ACS类型而异。不同表达的lncRNA,尤其是CCL15-CCL14,调控着moDCs的功能。因此,我们的研究为 lncRNAs 在 ACS 中的作用提供了新的见解,并表明 CCL15-CCL14 有可能被用作一种新的诊断标志物和治疗靶点。
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Dendritic cell-derived lncRNAs in patients with acute coronary syndrome

Long non-coding RNAs (lncRNAs) and dendritic cells (DC) play crucial roles in the development of acute coronary syndrome (ACS); however, the mechanisms remain unclear. To investigate this, we analysed the differentially expressed lncRNAs in monocyte-derived DCs (moDCs) from patients with ACS. Peripheral blood mononuclear cells were transformed into moDCs. Cellular morphology and expression levels of moDC-specific markers (CD80, CD86, CD11c, CD14 and HLA-DR) were analysed using electron microscopy (EM) and flow cytometry (FCM), respectively. Differentially expressed lncRNAs and their functions were predicted using gene sequencing, gene ontology and the Kyoto Encyclopedia of Genes and Genomes. The expression levels of markers, signalling pathway molecules (p-PI3K and p-AKT), inflammatory cytokines (IL-6 and IL-12p70) and target gene (C-C motif chemokine ligand (CCL) 15 and CCL14) were analysed by overexpression or silencing of candidate lncRNAs. EM revealed the cells to be suspended in dendritic pseudopodia. CD11c and HLA-DR were upregulated, while CD80 and CD86 were downregulated. Comparison between the UA versus ST group showed the highest number of differentially expressed lncRNAs (n = 113), followed by UA versus NST (n = 115), CON versus NST (n = 49) and CON versus ST (n = 35); however, the number was low for CON versus UA and ST versus NST groups. moDC-specific marker expression, signalling pathway molecules, inflammatory cytokines and CCL14 were upregulated following lentiviral overexpression of smart silencer-CCL15-CCL14; however, expression levels decreased following transfection with siRNA. The morphology, function and lncRNA expression of moDCs differ depending on the type of ACS. The differentially expressed lncRNAs, particularly CCL15-CCL14, regulate the function of moDCs. Thus, our study provides new insights regarding the role of lncRNAs in ACS and indicates the potential use of CCL15-CCL14 as a novel diagnostic marker and therapeutic target.

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期刊介绍: The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries. It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.
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