MiR-205 promotes endothelial progenitor cell angiogenesis and deep vein thrombosis recanalization and resolution by targeting PTEN to regulate Akt/autophagy pathway and MMP2 expression
MiR-205 promotes endothelial progenitor cell angiogenesis and deep vein thrombosis recanalization and resolution by targeting PTEN to regulate Akt/autophagy pathway and MMP2 expression
复制标题
MiR-205通过靶向PTEN调节Akt/自噬通路和MMP2表达促进内皮祖细胞血管生成和深静脉血栓再通和消退
DOI：
10.1111/jcmm.14739
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发表时间：
2019-10-21
影响因子：
5.3
通讯作者：
Li, Xiao-Qiang
中科院分区：
文献类型：
--
作者：
Sun, Li-Li;Xiao, Lun;Li, Xiao-Qiang
MicroRNA（MiRNA，MiR）是一类保守的非编码小RNA，影响转录后基因调控，在血管生成、增殖、凋亡、迁移和侵袭等过程中发挥重要作用。它们对于广泛的生理和病理过程是必不可少的，特别是对于血管疾病。然而，有关内皮祖细胞（EPCs）和深静脉血栓形成（DVT）的miRNA的数据仍然不完整。我们探索了调控内皮祖细胞血管生成和血栓溶解的miRNAs，并使用DVT模型、双荧光素酶报告基因测定、qRT-PCR、Western印迹、免疫荧光染色、流式细胞术分析、CCK-8测定、血管生成测定、伤口愈合和Transwell测定来分析其潜在机制。我们发现miR-205增强了EPCs归巢DVT部位的能力，促进血栓消退和再通，从而显著减少静脉血栓。此外，我们证明miR-205过表达显著增强EPCs体内和体外血管生成、迁移、侵袭、F-actin丝和增殖，并抑制细胞凋亡。相反，miR-205的下调在EPCs中起相反的作用。重要的是，这项研究表明，miR-205直接靶向PTEN调节Akt/自噬途径和MMP 2表达，随后在EPC功能和DVT再通和消退中发挥关键作用。这些结果阐明了miR-205在EPCs中的促血管生成作用，并将其确立为DVT治疗的潜在靶点。
MicroRNAs (MiRNAs, MiRs) represent a class of conserved small non-coding RNAs that affect post-transcriptional gene regulation and play a vital role in angiogenesis, proliferation, apoptosis, migration and invasion. They are essential for a wide range of physiological and pathological processes, especially for vascular diseases. However, data concerning miRNAs in endothelial progenitor cells (EPCs) and deep vein thrombosis (DVT) remain incomplete. We explored miRNAs that modulate angiogenesis in EPCs and thrombolysis, and analysed their underlying mechanisms using a DVT model, dual-luciferase reporter assay, qRT-PCR, Western blot, immunofluorescence staining, flow cytometry analysis, CCK-8 assay, angiogenesis assay, wound healing and Transwell assay. We found that miR-205 enhanced the homing ability of EPCs to DVT sites and promoted thrombosis resolution and recanalization, which significantly reduced venous thrombus. Additionally, we demonstrated that miR-205 overexpression significantly enhanced angiogenesis in vivo and in vitro, migration, invasion, F-actin filaments and proliferation in EPCs, and inhibited cell apoptosis. Conversely, down-regulation of miR-205 played the opposite role in EPCs. Importantly, this study demonstrated that miR-205 directly targeted PTEN to modulate the Akt/autophagy pathway and MMP2 expression, subsequently playing a key role in EPC function and DVT recanalization and resolution. These results elucidated the pro-angiogenesis effects of miR-205 in EPCs and established it as a potential target for DVT treatment.