MicroRNA Expression Profile of Neural Progenitor-Like Cells Derived from Rat Bone Marrow Mesenchymal Stem Cells under the Influence of IGF-1, bFGF and EGF

Int J Mol Sci. 2015 Apr 29;16(5):9693-718. doi: 10.3390/ijms16059693.

Abstract

Insulin-like growth factor 1 (IGF-1) enhances cellular proliferation and reduces apoptosis during the early differentiation of bone marrow derived mesenchymal stem cells (BMSCs) into neural progenitor-like cells (NPCs) in the presence of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). BMSCs were differentiated in three groups of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1, and (C) without growth factor. To unravel the molecular mechanisms of the NPCs derivation, microarray analysis using GeneChip miRNA arrays was performed. The profiles were compared among the groups. Annotated microRNA fingerprints (GSE60060) delineated 46 microRNAs temporally up-regulated or down-regulated compared to group C. The expressions of selected microRNAs were validated by real-time PCR. Among the 46 microRNAs, 30 were consistently expressed for minimum of two consecutive time intervals. In Group B, only miR-496 was up-regulated and 12 microRNAs, including the let-7 family, miR-1224, miR-125a-3p, miR-214, miR-22, miR-320, miR-708, and miR-93, were down-regulated. Bioinformatics analysis reveals that some of these microRNAs (miR-22, miR-214, miR-125a-3p, miR-320 and let-7 family) are associated with reduction of apoptosis. Here, we summarize the roles of key microRNAs associated with IGF-1 in the differentiation of BMSCs into NPCs. These findings may provide clues to further our understanding of the mechanisms and roles of microRNAs as key regulators of BMSC-derived NPC maintenance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cluster Analysis
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Epidermal Growth Factor / pharmacology*
  • Fibroblast Growth Factor 2 / pharmacology*
  • Gene Expression Profiling*
  • Gene Ontology
  • Gene Regulatory Networks / drug effects
  • Immunohistochemistry
  • Insulin-Like Growth Factor I / pharmacology*
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neural Stem Cells / cytology*
  • Oligonucleotide Array Sequence Analysis
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Reproducibility of Results
  • Software
  • Up-Regulation / drug effects
  • Up-Regulation / genetics

Substances

  • MicroRNAs
  • Fibroblast Growth Factor 2
  • Epidermal Growth Factor
  • Insulin-Like Growth Factor I