title: MicroRNA-22 induces endothelial progenitor cell senescence by targeting AKT3.
abstract: OBJECTIVE
  Endothelial progenitor cells (EPCs) play an important role in postnatal neovascularization. The number and function of EPCs declines as part of aging-associated senescence, thereby potentially contributing to vascular pathologies. Here, we investigated the significance and molecular mechanisms of microRNA-22 (miR-22) governing EPC senescence.
  
  
  METHODS
  EPCs were isolated from human circulating mononuclear cells from healthy young and aged volunteers. Cell senescence, proliferation, migration and tube formation ability were detected by SA-β-gal staining assay, MTT assay, transwell assay and Matrigel-based angiogenesis assay. Gene and protein expression were analyzed by qRT-PCR and Western blot respectively.
  
  
  RESULTS
  We found that miR-22 was upregulated in aged EPCs. Overexpression of miR-22 in young EPCs induced cell senescence, decreased proliferation and migration, and impaired angiogenesis in vitro. Conversely, silencing of endogenous miR-22 led to decreased cell senescence, increased proliferation and migration, and improved angiogenesis. AKT3 was identified as a direct target of miR-22, and restoration of AKT3 expression attenuated the effects of miR-22 in young EPCs.
  
  
  CONCLUSIONS
  Our results indicate that miR-22 induces EPC senescence by downregulating AKT3 expression, providing a potential novel target for the reversal of EPC dysfunction in angiogenesis.
authors.affiliation: Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zheng
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult
chemical_list: C548375:MIRN22 microRNA, human; D035683:MicroRNAs; C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt