Overexpression of miR-126 Promotes the Differentiation of Mesenchymal Stem Cells Toward Endothelial Cells via Activation of PI3K/Akt and MAPK/ERK Pathways and Release of Paracrine Factors

Biol Chem. 2013 Sep;394(9):1223-33. doi: 10.1515/hsz-2013-0107.


The endothelial cell (EC)-specific miRNA, miR-126, is known to promote angiogenesis in response to angiogenic factors by repressing negative regulators of signal transduction pathways; however, whether miR-126 might regulate the differentiation of stem cells toward endothelial lineage remains unknown. To answer this question, in this study mesenchymal stem cells (MSCs) harvested from C57BL/6 mouse bone marrow were transfected with miR-126 (MSCmiR-126) using recombinant lentiviral vectors. Results showed the para-secretion and the expression levels of phosphorylated PI3K p85, Akt, p38, ERK1 protein in the MSCmiR-126 group were dramatically increased when compared with the control group. With half culture medium refreshed every 3 days, a small number of 6-day-cultured MSCmiR-126 differentiated into endothelial-like cells and most of 9-day-cultured MSCmiR-126 formed a cobblestone-like structure. These differentiated cells evidently expressed EC-specific makers and possessed mature ECs function, while inhibition of paracrine factors suppressed the MSC-EC differentiation. Strikingly, the increased secretion of MSCmiR-126 and their endothelial-differentiated potential were deprived by using a PI3K or MEK chemical inhibitor. Our results suggest that overexpression of miR-126 agumenting the endothelial differentiation of MSCs might in part be attributable to the activation of PI3K/Akt and MAPK/ERK pathways and an increased release of paracrine factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism*
  • Enzyme Activation
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • MAP Kinase Signaling System / physiology*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / biosynthesis*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*


  • Intercellular Signaling Peptides and Proteins
  • MIRN126 microRNA, mouse
  • MicroRNAs
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt