Abstract
Aim:
To investigate whether nerve growth factor (NGF) induced angiogenesis of bone marrow mesenchymal stem cells (MSCs) and the underlying mechanisms.
Methods:
Bone marrow MSCs were isolated from femors or tibias of Sprague-Dawley rat, and cultured. The cells were purified after 3 to 5 passages, seeded on Matrigel-coated 24-well plates and treated with NGF. Tube formation was observed 24 h later. Tropomyosin-related kinase A (TrkA) and p75NTR gene expression was examined using PCR analysis and flow cytometry. Growth curves were determined via cell counting. Expression of VEGF and pAkt/Akt were analyzed with Western blot.
Results:
NGF (25, 50, 100 and 200 μg/L) promoted tube formation of MSCs. The tubular length reached the maximum of a 2.24-fold increase, when the cells were treated with NGF (50 μg/L). NGF (50 μg/L) significantly enhanced Akt phosphorylation. Pretreatment with the specific PI3K inhibitor LY294002 (10 μmol/L) blocked NGF-stimulated Akt phosphorylation, tube formation and angiogenesis. NGF (25–200 μg/L) did not affect the expression of TrkA and vascular endothelial growth factor (VEGF), but significantly suppressed the expression of p75NTR. NGF (50 μg/L) markedly increased the proliferation of MSCs.
Conclusion:
NGF promoted proliferation of MSCs and activated the PI3K/Akt signaling pathway, which may be responsible for NGF induction of MSC angiogenesis.
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Acknowledgements
This study was supported by the National Natural Science Foundation of China (Nos 30670868, 30770887, and 30770887/H0220), the Qianjiang Talent Scheme Foundation of Zhejiang Province (No 2009R10069) and the Key Lab of Traditional Chinese Medicine of Zhejiang Province (No ZK23812).
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Wang, Wx., Hu, Xy., Xie, Xj. et al. Nerve growth factor induces cord formation of mesenchymal stem cell by promoting proliferation and activating the PI3K/Akt signaling pathway. Acta Pharmacol Sin 32, 1483–1490 (2011). https://doi.org/10.1038/aps.2011.141
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DOI: https://doi.org/10.1038/aps.2011.141
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