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

• Published in: Molecular and cellular biochemistry 2008-03, Vol.310 (1-2), p.11-18
• Main Authors: Yu, Weihua, Chen, Zhenguang, Zhang, Jinli, Zhang, Lirong, Ke, Hui, Huang, Lihua, Peng, Yanwen, Zhang, Xiuming, Li, Shunong, Lahn, Bruce T, Xiang, Andy Peng
• Format: Article
• Language: English
• Subjects: Adipogenesis - drug effects; Biochemistry; Biomedical and Life Sciences; Cardiology; Cell Proliferation - drug effects; Enzyme Activation - drug effects; Humans; Kinases; Life Sciences; Medical Biochemistry; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - enzymology; Oncology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Protein Kinase Inhibitors - pharmacology; Protein Kinases - metabolism; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Ribosomal Protein S6 Kinases, 70-kDa - antagonists & inhibitors; Stem cells; Studies; Tissues; TOR Serine-Threonine Kinases; Transcription, Genetic - drug effects
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-007-9661-9

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 PPARγ₂ and C/EBPα, 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.