Proteomic analysis and microRNA expression profiling of plasma‐derived exosomes in primary immune thrombocytopenia
Proteomic analysis and microRNA expression profiling of plasma‐derived exosomes in primary immune thrombocytopenia
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DOI：
10.1111/bjh.17720
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发表时间：
2021-08
影响因子：
6.5
通讯作者：
Yunqi Sun;Yu Hou;Guiyue Meng;P. Han;Yajing Zhao;Haoyi Wang;Miao Xu;Yawen Wang;Jihua Qiu;J. Peng;L. Shao;Lu Sun;M. Hou
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文献类型：
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作者：
Yunqi Sun;Yu Hou;Guiyue Meng;P. Han;Yajing Zhao;Haoyi Wang;Miao Xu;Yawen Wang;Jihua Qiu;J. Peng;L. Shao;Lu Sun;M. Hou
外切体被释放到细胞外液中，并在自身免疫性疾病中成为重要的生物介质。血浆来源的外切体已被报道参与了原发性免疫性血小板减少症(ITP)的发病机制，但其蛋白质和miRNA的含量尚未完全阐明。通过对ITP患者和健康对照组血浆来源的外体进行蛋白质组学分析和RNA测序，我们发现了1个上调的外体蛋白(apo E，apoE)，6个下调的外体miRNAs(miR-584-5p，miR-4433a-5p，miR-4433b-3p，miR-6842-3p，miR-130b-5p和miR-222-3p)，以及10个上调的外体miRNAs(miR-29a-3p，miR-142-5p，miR-2-3p，miR-29b-3p，miR-501-3p，miR-144-5p，miR-192-5p，miR-182-5p，miR-182-5pMIR-363-3p和miR-96-5p)。免疫印迹进一步验证了ITP队列中升高的胞外体候选蛋白ApoE。通过实时定量聚合酶链式反应鉴定出3个差异表达的miRNAs(miR-584-5p、miR-142-5p和miR-29b-3p)。这项研究为外体蛋白和miRNAs的限制性签名提供了直接证据，这一签名将ITP与健康对照区分开来。这些结果需要在更大的独立ITP队列中进一步验证，这将为ITP循环外切体的潜在病理生理学意义提供洞察力。
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.