MicroRNA-195 regulates proliferation, migration, angiogenesis and autophagy of endothelial progenitor cells by targeting GABARAPL1.
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.
Department of Orthopedics Surgery, the First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, P.R. China mjw1997@126.com.
Jianwen
J
Mo
Department of Orthopedics Surgery, the First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, P.R. China.
Daifen
D
Zhang
Department of Orthopedics Surgery, the First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, P.R. China.
Renze
R
Yang
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D001343:Autophagy / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics; D020246:Venous Thrombosis / Q000473:pathology / Q000628:therapy*
D048868:Adaptor Proteins, Signal Transducing; C430503:GABARAPL1 protein, human; C552722:MIRN195 microRNA, human; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins
GABARAPL1; autophagy; endothelial progenitor cells; miR-195