Mol Cell Biochem 310:11 (2008)
Critical Role of Phosphoinositide 3-Kinase Cascade in Adipogenesis of Human Mesenchymal Stem Cells.
Weihua Yu, Zhenguang Chen, Jinli Zhang, Lirong Zhang, Hui Ke Lihua Huang, Yanwen Peng, Xiuming Zhang, Shunong Li Bruce T. Lahn, Andy Peng Xiang
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 PPARc2 and C/EBPa, 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.