Plasma exosomal RNAs have potential as both clinical biomarkers and therapeutic targets of dermatomyositis
Plasma exosomal RNAs have potential as both clinical biomarkers and therapeutic targets of dermatomyositis
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血浆外泌体 RNA 有潜力作为皮肌炎的临床生物标志物和治疗靶点
DOI：
10.1093/rheumatology/keab753
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发表时间：
2021-10-26
期刊：
影响因子：
5.5
通讯作者：
Zhu, Honglin
中科院分区：
文献类型：
--
作者：
Li, Liya;Zuo, Xiaoxia;Zhu, Honglin
目的糖尿病以骨骼肌无力和皮肤损害为特征。血浆外泌体（EXOs）含有蛋白质、RNA、DNA和脂质货物，并且在细胞之间转移。如果彻底研究，血浆EXO RNA可能会提高我们对DM发病机制的理解。我们的目的是确定潜在的新的生物标志物和治疗糖尿病的目标。方法采用Illumina HiSeq 3000测序平台分析血浆EXO的RNA（mRNA、miRNA和lncRNA）谱。进行差异表达（DE）RNA和生物信息学分析。用血浆EXO、雷帕霉素或IFN-β刺激人骨骼肌成肌细胞（HSkMCs）。采用实时荧光定量PCR和Western blot方法检测相关基因和蛋白。结果在DM血浆EXO中共鉴定出689种DE mRNA、53种DE miRNA和452种DE lncRNA。生物信息学分析表明，血浆EXO主要由CD 8 + T细胞、调节性T细胞和自然杀伤细胞分泌。DE miRNAs参与自噬、TGF-β和Wnt信号通路。三种DE miRNAs（hsa-miR-125 a-3 p、hsa-miR-1246和hsa-miR-3614- 5 p）与血清学指标、器官受累和肌炎特异性自身抗体相关。DE lncRNA参与自噬、IFN-β产生和mTOR信号传导。DM血浆EXO可通过调节3种miRNAs（hsa-miR-125 a-3 p、hsa-miR-1246和hsa-miR-3614- 5 p）和3种lncRNAs（ENST 0000584157.1、ENST 00000523380.1和ENST 0000560054.1）诱导HSkMCs发生自噬，形成自噬网络，在肌肉损伤中发挥作用。结论本研究提供了DM血浆EXO中不同RNA表达谱的概况，并验证了部分miRNA作为潜在的生物标志物和治疗靶点的可能性。这些发现为更深入地探索糖尿病患者血浆EXO提供了重要线索。
Objectives DM is characterized by skeletal muscle weakness and cutaneous manifestations. Plasma exosomes (EXOs) contain proteins, RNAs, DNA, and lipid cargoes and are transferred among cells. If thoroughly investigated, plasma EXO RNAs could potentially improve our understanding of DM pathogenesis. We aimed to identify potential new biomarkers and therapeutic targets for DM. Methods The RNA (mRNA, miRNA and lncRNA) profiles of plasma EXOs were evaluated by sequencing on the Illumina HiSeq 3000 platform. Differentially expressed (DE) RNAs and bioinformatic analyses were performed. Human skeletal muscle myoblasts cells (HSkMCs) were stimulated with plasma EXOs, rapamycin or IFN-beta. Real-time PCR and western blot analysis were used to detect related genes and proteins. Results A total of 689 DE mRNAs, 53 DE miRNAs and 452 DE lncRNAs were identified in DM plasma EXOs. Bioinformatic analysis inferred that plasma EXOs were secreted mainly by CD8+ T cells, regulatory T cells and natural killer cells. The DE miRNAs participated in the autophagy, TGF-beta and Wnt signalling pathways. Three DE miRNAs (hsa-miR-125a-3p, hsa-miR-1246 and hsa-miR-3614-5p) were correlated with serological indices, organ involvement and myositis-specific autoantibodies. The DE lncRNAs participated in autophagy, IFN-beta production and mTOR signalling. DM plasma EXOs can induce autophagy in HSkMCs by regulating three miRNAs (hsa-miR-125a-3p, hsa-miR-1246 and hsa-miR-3614-5p) and three lncRNAs (ENST00000584157.1, ENST00000523380.1 and ENST00000560054.1), which formed an autophagy network, playing a role in muscle damage. Conclusion Our study provides an overview of distinct RNA profiles in DM plasma EXOs, and verified some miRNAs as potential biomarkers and therapeutic targets. The findings provide important clues for more in-depth explorations of plasma EXOs in DM.