Journal
CELL AND TISSUE BANKING
Volume 23, Issue 3, Pages 459-472Publisher
SPRINGER
DOI: 10.1007/s10561-021-09956-2
Keywords
Insulin growth factor-1; Neural progenitor cells; Akt; mTOR; Apoptosis; Proliferation
Categories
Funding
- National Natural Science Foundation of China [81100929]
- Medical Research Innovation Project Plan of Sichuan Province [Q15032]
- Science & Technology Project of Nanchong City [18SXHZ0374]
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The study demonstrated that IGF-I overexpression inhibited cell apoptosis and enhanced cell migration in NPCs. The Akt/mTOR/p70S6K signaling cascade was found to be present in NPCs, and IGF-I overexpression significantly activated this cascade, while rapamycin addition inhibited its expression. These results indicate that IGF-I may enhance cell proliferation and differentiation through Akt/mTOR/p70S6K signaling cascade, potentially playing a role in spinal cord repair and remodeling after injury.
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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