Mesenchymal stem cells promote endothelial progenitor cell proliferation by secreting insulin‑like growth factor‑1

Mol Med Rep. 2017 Aug;16(2):1502-1508. doi: 10.3892/mmr.2017.6741. Epub 2017 Jun 9.

Abstract

Bone marrow mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) interact with each other. EPCs are able to promote the self‑renewal of MSCs as niche cells in murine bone marrow, and MSCs are able to promote EPC proliferation in vitro in a co‑culture system. It has previously been reported that MSCs can secrete insulin‑like growth factor‑1 (IGF‑1), which serves critical functions in EPC proliferation. However, the mechanism underlying the IGF‑1‑mediated proliferation of EPCs remains unclear. The aim of the present study was to reveal the molecular mechanisms regulating this process. The effects of IGF‑1, which is secreted by MSCs, on EPC proliferation via the PI3K/Akt signaling pathway were examined by MTT assay, reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The present study treated EPCs with various concentrations of IGF‑1. The results demonstrated that IGF‑1 significantly induced the proliferation of cultured EPCs. However, this effect was offset by treatment with the phosphatidylinositol 3‑kinase (PI3K) inhibitor LY294002. These results indicated that the pro‑proliferative effects of IGF‑1 are mediated in response to the PI3K/protein kinase B signaling pathway.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Chromones / pharmacology
  • Coculture Techniques
  • Endothelial Progenitor Cells / cytology*
  • Endothelial Progenitor Cells / drug effects
  • Endothelial Progenitor Cells / metabolism
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • Mice, Inbred C57BL
  • Morpholines / pharmacology
  • Phosphatidylinositol 3-Kinase / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction

Substances

  • Chromones
  • Morpholines
  • RNA, Messenger
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Insulin-Like Growth Factor I
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt