Critical role of phosphoinositide 3-kinase cascade in adipogenesis of human mesenchymal stem cells

Mol Cell Biochem. 2008 Mar;310(1-2):11-8. doi: 10.1007/s11010-007-9661-9. Epub 2007 Dec 2.

Abstract

Mesenchymal stem cells (MSCs) are multipotent stem cells capable of differentiating into adipocytes in the presence of a hormone cocktail. These cells thus provide a promising model for studying the early events of adipogenesis. Here, we examine the involvement of the PI3K/Akt and mTOR/p70S6K signaling pathways in human MSC adipogenesis. We found that the two pathways were strongly activated with a similar temporal profile under the adipogenesis-inducing hormone cocktail and this activation could be blocked by LY294002, a specific inhibitor of PI3K. Furthermore, rapamycin, a specific inhibitor of mTOR, blocked the activation of mTOR/p70S6K but not PI3K/Akt. Both LY294002 and rapamycin severely suppressed lipid accumulation, as well as the expression of adipogenic markers, including PPAR gamma 2 and C/EBP alpha, two master adipogenic transcription factors. Together, these data indicate that the mTOR/p70S6K pathway acts downstream of the PI3K/Akt pathway in mediating the adipogenic conversion of MSCs. In conclusion, our data suggest that the PI3K/Akt and mTOR/p70S6K signaling pathways are essential for adipogenesis of human MSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis* / drug effects
  • Cell Proliferation / drug effects
  • Enzyme Activation / drug effects
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / enzymology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Ribosomal Protein S6 Kinases, 70-kDa / antagonists & inhibitors
  • TOR Serine-Threonine Kinases
  • Transcription, Genetic / drug effects

Substances

  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa