Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Health Care System, Ha Noi 10000, Vietnam.
Tissue Repair and Translational Physiology Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia.
Int J Mol Sci. 2020 Feb 8;21(3):1141. doi: 10.3390/ijms21031141.
Extracellular membrane vesicles (EVs) have emerged as potential candidates for diagnostics and therapeutics. We have previously reported that keratinocytes release three types of EVs into the extracellular environment. Importantly, those EVs contain a large number of microRNAs (miRNAs) as cargo. In this study, we examined the expression level of keratinocyte-derived EV miRNAs, their target genes and potential functions. Next generation sequencing results showed that over one hundred miRNAs in each EV subtype exhibited greater than 100 reads per million (RPM), indicating a relatively high abundance. Analysis of the miRNAs with the highest abundance revealed associations with different keratinocyte cell sources. For instance, hsa-miR-205 was associated with the HaCaT cells whereas hsa-miR-21, hsa-miR-203, hsa-miR-22 and hsa-miR-143 were associated with human primary dermal keratinocytes (PKCs). Additionally, functional annotation analysis of genes regulated by those miRNAs, especially with regard to biological processes, also revealed cell-type-specific associations with either HaCaTs or PKCs. Indeed, EV functional effects were related to their parental cellular origin; specifically, PKC-derived EVs influenced fibroblast migration whereas HaCaT-derived EVs did not. In addition, the data in this current study indicates that keratinocyte-derived EVs and/or their cargoes have potential applications for wound healing.
细胞外膜囊泡 (EVs) 已成为诊断和治疗的潜在候选物。我们之前曾报道过，角质形成细胞会将三种类型的 EV 释放到细胞外环境中。重要的是，这些 EV 中含有大量的 microRNAs (miRNAs) 作为货物。在这项研究中，我们检查了角质形成细胞来源的 EV miRNAs 的表达水平、它们的靶基因和潜在功能。下一代测序结果表明，每种 EV 亚型中的超过一百种 miRNAs 的每百万读数 (RPM) 大于 100，表明相对丰度较高。对丰度最高的 miRNAs 的分析揭示了与不同角质形成细胞来源的关联。例如，hsa-miR-205 与 HaCaT 细胞相关，而 hsa-miR-21、hsa-miR-203、hsa-miR-22 和 hsa-miR-143 与原代人皮肤角质形成细胞 (PKCs) 相关。此外，受这些 miRNAs 调控的基因的功能注释分析，特别是关于生物学过程的分析，也揭示了与 HaCaTs 或 PKCs 具有细胞类型特异性的关联。事实上，EV 的功能效应与其亲代细胞来源有关；具体而言，PKC 衍生的 EV 影响成纤维细胞迁移，而 HaCaT 衍生的 EV 则没有。此外，本研究的数据表明，角质形成细胞来源的 EVs 和/或其货物在伤口愈合方面具有潜在的应用价值。
