Department of Rheumatology and Immunology, Xiangya Hospital of Central South University.
Department of Rheumatology and Immunology, the Third Xiangya Hospital, Central South University.
Rheumatology (Oxford). 2022 May 30;61(6):2672-2681. doi: 10.1093/rheumatology/keab753.
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.
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-β. Real-time PCR and western blot analysis were used to detect related genes and proteins.
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-β 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-β 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.
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.
DM 的特征在于骨骼肌无力和皮肤表现。血浆外泌体（EXO）包含蛋白质、RNA、DNA 和脂质货物，并在细胞间传递。如果进行深入研究，血浆 EXO RNA 有可能增进我们对 DM 发病机制的理解。我们旨在寻找 DM 的潜在新生物标志物和治疗靶点。
通过在 Illumina HiSeq 3000 平台上进行测序，评估血浆 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（HSkMC）。实时 PCR 和 Western blot 分析用于检测相关基因和蛋白。
在 DM 血浆 EXO 中鉴定出 689 个差异表达 mRNA、53 个差异表达 miRNA 和 452 个差异表达 lncRNA。生物信息学分析推断，血浆 EXO 主要由 CD8+T 细胞、调节性 T 细胞和自然杀伤细胞分泌。DE miRNA 参与自噬、TGF-β 和 Wnt 信号通路。三个 DE miRNA（hsa-miR-125a-3p、hsa-miR-1246 和 hsa-miR-3614-5p）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。DM 血浆 EXO 可通过调节三个 miRNA（hsa-miR-125a-3p、hsa-miR-1246 和 hsa-miR-3614-5p）和三个 lncRNA（ENST00000584157.1、ENST00000523380.1 和 ENST00000560054.1）在 HSkMC 中诱导自噬，形成自噬网络，在肌肉损伤中发挥作用。
本研究提供了 DM 血浆 EXO 中独特 RNA 谱的概述，并验证了一些 miRNA 作为潜在的生物标志物和治疗靶点。研究结果为更深入探索 DM 中的血浆 EXO 提供了重要线索。
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