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

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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 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.

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Abbreviations

PI3K:

Phosphoinositide 3-kinase

mTOR:

Mammalin target of rapamycin

MSC:

Mesenchymal stem cell

LPL:

Lipoprotein lipase

αP2 :

Adipocyte-specific fatty acid-binding protein

PPARγ:

Peroxisome proliferator-activated receptor γ

C/EBPα:

CCAAT/enhancer binding protein α

AIM:

Adipocyte induction medium

AMM:

Adipocyte maintenance medium

PCNA:

Proliferating cell nuclear antigen

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Acknowledgments

We thank Bao-Feng Ma, Jia-Qing Zhang and Ai-Xia Zhang for helpful discussion, and Wen-Jun Xin for technical support in immunoblotting. This work was supported by The National Natural Science Foundation of China, No. 30100188 and 30571891, and The Scientific and Technological Plan Projects of Guangzhou City, No. 2006J1-C0271.

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Correspondence to Andy Peng Xiang.

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Yu, W., Chen, Z., Zhang, J. et al. Critical role of phosphoinositide 3-kinase cascade in adipogenesis of human mesenchymal stem cells. Mol Cell Biochem 310, 11–18 (2008). https://doi.org/10.1007/s11010-007-9661-9

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  • DOI: https://doi.org/10.1007/s11010-007-9661-9

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