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.

中文翻译：

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mTOR复合物在IGF-1诱导的DPSCs神经分化中的作用。

最近的研究表明，IGF-1调节牙髓干细胞（DPSC）的多能分化。尽管已证明mTOR途径的激活是IGF-1诱导的多能分化的原因，但IGF-1–mTOR途径诱导DPSC的神经分化的机制仍不清楚。在我们的研究中，我们证明了0-10 ng / mL IGF-1对DPSC的增殖没有明显影响，但是IGF-1仍以剂量依赖的方式增强了DPSC的神经分化。同时，我们发现磷酸化的mTOR被上调，表明mTOR参与了该过程。雷帕霉素是mTOR活性的抑制剂，可以逆转由IGF-1刺激的DPSC的作用。接下来，我们研究了两种已知的mTOR复合体mTORC1和mTORC2的作用，在DPSCs的神经分化中。我们发现抑制mTORC1可以严重限制DPSCs的神经分化。但是，抑制mTORC2具有相反的作用。当rictor和mTOR均被抑制时，后一种效应消失，表明mTORC2效应与mTORC1有关。这项研究扩大了mTOR在IGF-1调控的DPSCs神经分化中的作用。