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High density lipoprotein cholesterol promotes the proliferation of bone-derived mesenchymal stem cells via binding scavenger receptor-B type I and activation of PI3K/Akt, MAPK/ERK1/2 pathways

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Abstract

High-density lipoprotein (HDL) possesses protective properties in cardiovascular diseases. However, the effect of HDL on the mesenchymal stem cells (MSCs), which could be mobilized to the damaged myocardial tissue, has not been well elucidated yet. In the current study, we investigated the effect of HDL on the proliferation of MSCs so as to reveal its molecular mechanisms. MSCs derived from rats were treated with HDL in different concentrations and for different periods. The proliferation of MSCs was measured with MTT and BrdU cell proliferation assay. The phosphorylation of Akt, ERK1/2 and the expression of p21 were evaluated by Western blotting. After the activity of respective pathways was down-regulated by the specific inhibitor and the gene of scavenger receptor-B type I (SR-BI) was knocked down by RNA interference, BrdU assay was performed to examine this effect of HDL on MSCs. We found that the proliferation of MSCs induced by HDL, in a time- and concentration-dependent manner, was the phosphorylation of Akt- and ERK1/2-dependent, which was significantly attenuated by the specific inhibitor to respective pathways. Moreover, MAPK/ERK1/2 pathway exerted a more dominating effect on this process. SR-BI contributed to HDL-induced proliferation of MSCs, which was effectively abolished by the silencing of SR-BI. The results suggested that HDL was capable of improving MSCs proliferation, in which MAPK/ERK1/2 and PI3K/Akt pathways involved and SR-BI played a critical role as well.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (Project Nos. 81100145, 30901383 and 81000043), Shuguang Project of Shanghai (Project No. 08SG03), and Research Fund for the Doctoral Program of Higher Education of China (Project No. 20100071120072).

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Authors and Affiliations

  1. Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Jianfeng Xu, Juying Qian, Xinxing Xie, Li Lin, Jianying Ma, Zheyong Huang, Mingqiang Fu, Yunzeng Zou & Junbo Ge

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  1. Jianfeng Xu
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  2. Juying Qian
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  3. Xinxing Xie
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  4. Li Lin
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  8. Yunzeng Zou
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  9. Junbo Ge
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Correspondence to Juying Qian or Junbo Ge.

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Jianfeng Xu and Juying Qian contributed equally to this study.

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Xu, J., Qian, J., Xie, X. et al. High density lipoprotein cholesterol promotes the proliferation of bone-derived mesenchymal stem cells via binding scavenger receptor-B type I and activation of PI3K/Akt, MAPK/ERK1/2 pathways. Mol Cell Biochem 371, 55–64 (2012). https://doi.org/10.1007/s11010-012-1422-8

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