MicroRNA-195 regulates proliferation, migration, angiogenesis and autophagy of endothelial progenitor cells by targeting GABARAPL1.
MicroRNA-195 regulates proliferation, migration, angiogenesis and autophagy of endothelial progenitor cells by targeting GABARAPL1.
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DOI：
10.1042/bsr20160139
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发表时间：
2016-10
影响因子：
4
通讯作者：
Yang R
中科院分区：
文献类型：
--
作者：
Mo J;Zhang D;Yang R
深静脉血栓（DVT）是一种常见的静脉血栓。深静脉血栓相关血栓的成功清除对深静脉血栓的治疗至关重要。内皮祖细胞（EPCs）已成为解决dvt相关血栓的有希望的治疗选择；然而，内皮祖细胞的临床应用面临诸多挑战。在本研究中，我们采用实时荧光定量PCR （qRT-PCR）检测了miR-582、miR-195和miR-532在缺氧或常氧条件下的表达，结果显示，在缺氧条件下，miR-195在人EPCs （hEPCs）中增加的倍数最高。进而探讨miR-195在改善EPCs功能中的作用及调控机制。为了研究miR-195抑制对hepc细胞自噬的影响，采用western blotting检测自噬相关基因LC3B和beclin1的表达，TEM观察自噬体的形成。结果表明，抑制miR-195的表达可促进hepc的自噬。此外，我们还研究了miR-195在缺氧条件下对hepc增殖、迁移和血管生成的作用。结果显示，miR-195抑制可促进缺氧条件下hepc细胞增殖、迁移和血管生成。此外，GABA型A受体相关蛋白如1 （GABARAPL1）被确定为miR-195的定向靶点，GABARAPL1沉默可以降低miR-195敲低对缺氧条件下hepc细胞增殖、迁移、血管生成和自噬的影响。综上所述，这些结果表明miR-195通过靶向GABARAPL1调控hepc的细胞增殖、迁移、血管生成和自噬。
Deep vein thrombosis (DVT) is a common type of venous thrombosis. Successful resolution of DVT-related thrombi is important in the treatment of DVT. Endothelial progenitor cells (EPCs) have emerged as a promising therapeutic choice for DVT-related thrombus resolution; however, the clinical application of EPCs faces many challenges. In the present study, the expression of miR-582, miR-195 and miR-532 under hypoxic or normoxic conditions was measured using quantitative real-time PCR analysis (qRT-PCR) and the results showed that the increased fold of miR-195 was highest in human EPCs (hEPCs) under hypoxic conditions. Then the role and regulating mechanism of miR-195 in improving the function of EPCs was investigated. To investigate the effect of miR-195 inhibition on the autophagy of hEPCs, the expression of the autophagy-related genes LC3B and beclin1 was examined using western blotting, and the formation of autophagosomes was observed using TEM. The results indicated that the inhibition of miR-195 expression could promote autophagy of hEPCs. In addition, we investigated the role of miR-195 on the proliferation, migration and angiogenesis of hEPCs under hypoxia. The results revealed that miR-195 inhibition promotes cell proliferation, migration and angiogenesis of hEPCs under hypoxia. Furthermore, GABA type A receptor associated protein like 1 (GABARAPL1) was identified as a directed target of miR-195 and GABARAPL1 silencing could decrease the effect of miR-195 knockdown on cell proliferation, migration, angiogenesis and autophagy of hEPCs under hypoxia. Together, these results indicate that miR-195 regulates cell proliferation, migration, angiogenesis and autophagy of hEPCs by targeting GABARAPL1.