Role of mTOR complex in IGF-1 induced neural differentiation of DPSCs
- 50 Downloads
Recent studies have demonstrated that IGF-1 modulates the pluripotent differentiation of dental pulp stem cells (DPSCs). Although mTOR pathway activation has been showed as responsible for IGF-1 induced pluripotent differentiation, the mechanism that the IGF-1–mTOR pathway induces the neural differentiation of DPSCs is still unclear. In our research, we have demonstrated that 0–10 ng/mL IGF-1 had no obvious effect on the proliferation of DPSCs, but IGF-1 nonetheless enhances the neural differentiation of DPSCs in a dose-dependent manner. Simultaneously, we found that phosphorylated mTOR was up-regulated, which indicated the involvement of mTOR in the process. Rapamycin, an inhibitor of mTOR activity, can reverse the effect of DPSCs stimulated by IGF-1. Next, we studied the role of mTORC1 and mTORC2, two known mTOR complexes, in the neural differentiation of DPSCs. We found that inhibition of mTORC1 can severely restricts the neural differentiation of DPSCs. However, inhibition of mTORC2 has the opposite effect. This latter effect disappears when both rictor and mTOR are inhibited, showing that the mTORC2 effect is mTORC1 dependent. This study has expanded the role of mTOR in DPSCs neural differentiation regulated by IGF-1.
KeywordsDental pulp stem cells (DPSCs) Insulin-like growth factor 1 (IGF-1) mTOR signaling Neural differentiation
This study was supported by Chinese National Natural Science Foundation of China Grant (Nos. 81500809, 81501076).
- Ebrahimi-Barough S, Hoveizi E, Yazdankhah M, Ai J, Khakbiz M, Faghihi F, Tajerian R, Bayat N (2017) Inhibitor of PI3 K/Akt signaling pathway small molecule promotes motor neuron differentiation of human endometrial stem cells cultured on electrospun biocomposite polycaprolactone/collagen scaffolds. Mol Neurobiol 54:2547–2554CrossRefGoogle Scholar
- Korzheneskiy DE, Kirik OV, Alekseyeva OS (2014) Nestin expression in ependymal cells of lateral ventricles of the rat brain in aging. Morfologiia 146:70–72Google Scholar
- Luo L, He Y, Wang X, Key B, Lee BH, Li H, Ye Q (2018a) Potential roles of dental pulp stem cells in neural regeneration and repair. Stem Cells Int 2018:1731289Google Scholar
- Luo Y, Xu W, Li G, Cui W (2018b) Weighing in on mTOR complex 2 signaling: the expanding role in cell metabolism. Oxidative Med Cell Longev 2018:7838647Google Scholar
- Ray S, Darbre PD (2011) Crosstalk with insulin and dependence on PI3 K/Akt/mTOR rather than MAPK pathways in upregulation of basal growth following long-term oestrogen deprivation in three human breast cancer cell lines. Horm Mol Biol Clin Investig 5:53–65Google Scholar
- Yue X, Zhifeng G, Biyu S, Guofeng X, Tianqiu Z, Jinxia J, Jing X, Suzhe L, Man L, Wei T, Guijuan F, Aimin S, Liren L (2013) Roles of Wnt/beta-catenin signaling in retinal neuron-like differentiation of bone marrow mesenchymal stem cells from nonobese diabetic mice. J Mol Neurosci 49:250–261CrossRefGoogle Scholar
- Zhou L, Tu J, Fang G, Deng L, Gao X, Guo K, Kong J, Lv J, Guan W, Yang C (2018) Combining PLGA scaffold and MSCs for brain tissue engineering: a potential tool for treatment of brain injury. Stem cells Int 2018:5024175Google Scholar