Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Department of Pain, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Br J Haematol. 2021 Sep;194(6):1045-1052. doi: 10.1111/bjh.17720. Epub 2021 Aug 1.
Exosomes are released into extracellular fluids and have emerged as vital biological mediators in autoimmune diseases. Plasma-derived exosomes have been reported to take part in the pathogenesis of primary immune thrombocytopenia (ITP), but the protein and miRNA cargoes have not been entirely elucidated. Via proteomic analysis and RNA sequencing on plasma-derived exosomes from ITP patients and healthy controls, we found one upregulated exosomal protein (apolipoprotein E, ApoE), six downregulated exosomal miRNAs (miR-584-5p, miR-4433a-5p, miR-4433b-3p, miR-6842-3p, miR-130b-5p and miR-222-3p), and 10 upregulated exosomal miRNAs (miR-29a-3p, miR-142-5p, miR-16-2-3p, miR-29b-3p, miR-501-3p, miR-144-5p, miR-192-5p, miR-182-5p, miR-363-3p and miR-96-5p) in ITP patients. The elevated exosomal protein candidate ApoE in the ITP cohort was further validated using western blot. Via quantitative real-time polymerase chain reaction assays, three differentially expressed miRNAs (miR-584-5p, miR-142-5p and miR-29b-3p) were identified. This study provides direct evidence for a restricted signature of exosomal protein and miRNAs which distinguishes ITP from healthy controls. The results require further validation in larger independent ITP cohorts, which will provide insights into the potential pathophysiological significance of circulating exosomes in ITP.
外泌体被释放到细胞外液中,已成为自身免疫性疾病中重要的生物介质。已有报道称,血浆来源的外泌体参与原发性免疫性血小板减少症(ITP)的发病机制,但蛋白质和 miRNA 货物尚未完全阐明。通过对 ITP 患者和健康对照者血浆来源的外泌体进行蛋白质组学分析和 RNA 测序,我们发现一个上调的外泌体蛋白(载脂蛋白 E,ApoE)、六个下调的外泌体 miRNA(miR-584-5p、miR-4433a-5p、miR-4433b-3p、miR-6842-3p、miR-130b-5p 和 miR-222-3p)和 10 个上调的外泌体 miRNA(miR-29a-3p、miR-142-5p、miR-16-2-3p、miR-29b-3p、miR-501-3p、miR-144-5p、miR-192-5p、miR-182-5p、miR-363-3p 和 miR-96-5p)在 ITP 患者中。在 ITP 队列中,用 Western blot 进一步验证了升高的外泌体蛋白候选物 ApoE。通过实时定量聚合酶链反应检测,鉴定出三个差异表达的 miRNA(miR-584-5p、miR-142-5p 和 miR-29b-3p)。本研究为区分 ITP 与健康对照的外泌体蛋白和 miRNA 的受限特征提供了直接证据。这些结果需要在更大的独立 ITP 队列中进一步验证,这将为循环外泌体在 ITP 中的潜在病理生理意义提供新的见解。