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Insulin growth factor-1 enhances proliferation and inhibits apoptosis of neural progenitor cells by phosphorylation of Akt/mTOR/p70S6K molecules and triggering intrinsic apoptosis signaling pathway

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Abstract

Neural progenitor cells (NPCs) transplantation is known as a potential strategy for treating spinal cord injury (SCI). This study aimed to investigate effects of insulin growth factor-1 (IGF-I) on NPCs proliferation and clarify associated mechanisms. NPCs isolated from T8-T10 segmental spinal cord tissues of rats were cultured and identification. Then, lentivirus packing plasmids containing IGF-I was constructed and used for NPCs infection. Cell proliferation was evaluated by detecting 5-Bromodeoxyuridine (BrdU) expression in NPCs, cell differentiation was detected using double-labeling immunofluorescence staining while cell apoptosis was detected using TUNEL assay. In addition, the signal expression of Akt/mTOR/p70S6K in NPCs cells were investigated using immunofluorescence staining and western blot assay. The experimental group was defined as pCMV-IGF-I group, while the negative control group was defined as pCMV-LacZ group. Cells infected with pCMV-IGF-I lentivirus followed by addition of 100 mg/ml rapamycin were defined as pCMV-IGF-I + Rapa group. NPCs were successfully isolated, identified and cultured. IGF-I overexpression significantly inhibited cell apoptosis and enhanced cell migration. Akt/mTOR/ p70S6K signaling cascade was proved to be present in NPCs, IGF-I overexpression significantly activated Akt/mTOR/p70S6K signaling cascade, while rapamycin addition inhibited its expression. Also, the activated Akt/mTOR/p70S6K signal cascade induced by IGF-I significantly enhanced BrdU expression and inhibited cell apoptosis, and promoted the differentiation of NPC into the neuronal system. However, the rapamycin addition inhibited the cell response induced by IGF-I overexpression. IGF-I overexpression could enhance cell proliferation, inhibit cell apoptosis and promote their differentiation into neuronal systems by activating Akt/mTOR/p70S6K signaling cascade in vitro, indicating that the Akt/mTOR/p70S6K signaling cascade may be the potentially mechanism for the endogenous repair and remodeling of spinal cord after injury.

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Acknowledgements

This study was financially supported by the National Natural Science Foundation of China (Grant No. 81100929), Medical Research Innovation Project Plan of Sichuan Province (Grant No. Q15032) and Science & Technology Project of Nanchong City (18SXHZ0374).

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Author notes

  1. Bo Zhang, Lingyun Hu and Jianying Zhang have equally contributed to this work.

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Nanchong Central Hospital, the Second Clinical Medical College of North Sichuan Medical College, Nanchong, 637000, Sichuan, China

    Bo Zhang, Lingyun Hu, Hui Wu, Wei Li & Lin Gou

  2. Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China

    Lingyun Hu & Hao Liu

  3. Department of Radiology, Nanchong Central Hospital, the Second Clinical Medical College of North Sichuan Medical College, Nanchong, Sichuan, 637000, China

    Jianying Zhang

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  1. Bo Zhang
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  2. Lingyun Hu
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  4. Hui Wu
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  5. Wei Li
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  7. Hao Liu
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Correspondence to Hao Liu.

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Zhang, B., Hu, L., Zhang, J. et al. Insulin growth factor-1 enhances proliferation and inhibits apoptosis of neural progenitor cells by phosphorylation of Akt/mTOR/p70S6K molecules and triggering intrinsic apoptosis signaling pathway. Cell Tissue Bank 23, 459–472 (2022). https://doi.org/10.1007/s10561-021-09956-2

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  • DOI: https://doi.org/10.1007/s10561-021-09956-2

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