溶菌酶与循环RNA、细胞外囊泡和慢性应激的关联

BBA clinical Pub Date : 2017-06-01 DOI:10.1016/j.bbacli.2016.12.003

Sarah K. Abey , Yuana Yuana , Paule V. Joseph , Natnael D. Kenea , Nicolaas H. Fourie , LeeAnne B. Sherwin , Gregory E. Gonye , Paul A. Smyser , Erin S. Stempinski , Christina M. Boulineaux , Kristen R. Weaver , Christopher K.E. Bleck , Wendy A. Henderson

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引用次数: 23

摘要

应激已被证明对炎症有影响，但潜在的细胞-细胞通讯机制尚不清楚。我们假设慢性应激患者的循环rna和细胞外囊泡(EVs)含有在细胞修复中起功能作用的信号。方法比较肠易激综合征患者和对照组的血液转录组，以确定信号通路和效应物。分离血浆EVs(大小排斥层析)并对效应物的存在进行表征(免疫金标记-电镜)。基于转录组通路和ev标记，在人结肠上皮CRL-1790细胞中测试了溶菌酶对细胞迁移的影响，并与迁移诱导剂CXCL12的作用进行了比较(伤口试验)。研究了溶菌酶对血清饥饿和抓伤后存活细胞免疫相关mRNA和蛋白水平的影响。结果血液转录组显示了吡哆醛5 '磷酸挽救、嘧啶核糖核苷酸挽救途径、动脉粥样硬化和以膜CD9和细胞外溶菌酶为效应的细胞运动信号。血浆EVs显示有CD9、粘蛋白和溶菌酶标记。这是首次在血浆ev上发现溶菌酶。在CRL-1790细胞中，溶菌酶诱导迁移并修复划伤和CXCL12。在伤后无血清培养基中，不论有无溶菌酶，血清饥饿和抓伤后存活的细胞免疫mRNA和蛋白的表达都发生了变化:CD9、IL8、IL6 mRNA和CD9、NT5E、PD-L1蛋白。结论慢性应激患者血浆EVs和循环rna中存在修复和炎症信号。本研究强调了循环rna和EVs在应激中的作用。

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Lysozyme association with circulating RNA, extracellular vesicles, and chronic stress

Background

Stress has demonstrated effects on inflammation though underlying cell-cell communication mechanisms remain unclear. We hypothesize that circulating RNAs and extracellular vesicles (EVs) in patients with chronic stress contain signals with functional roles in cell repair.

Methods

Blood transcriptome from patients with Irritable Bowel Syndrome versus controls were compared to identify signaling pathways and effectors. Plasma EVs were isolated (size-exclusion chromatography) and characterized for effectors' presence (immunogold labelling-electron microscopy). Based on transcriptome pathways and EV-labelling, lysozyme's effects on cell migration were tested in human colon epithelial CRL-1790 cells and compared to the effects of CXCL12, a migration inducer (wound assay). The effect of lysozyme on immune-linked mRNA and protein levels in cells which survived following serum starvation and scratch wound were investigated (NanoString).

Results

Blood transcriptomes revealed pyridoxal 5’phosphate salvage, pyrimidine ribonucleotides salvage pathways, atherosclerosis, and cell movement signaling with membrane CD9 and extracellular lysozyme as effectors. Plasma EVs showed labelling with CD9, mucins, and lysozyme. This is the first identification of lysozyme on plasma EVs. In CRL-1790 cells, lysozyme induced migration and repaired scratch wound as well as CXCL12. Immune mRNA and protein expressions were altered in cells which survived following serum starvation and scratch wound, with or without lysozyme in serum-free media post-wounding: CD9, IL8, IL6 mRNAs and CD9, NT5E, PD-L1 proteins.