期刊
EXPERIMENTAL AND THERAPEUTIC MEDICINE
卷 22, 期 5, 页码 -出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/etm.2021.10700
关键词
spinal cord injury; insulin-like growth factor 1; autophagy; PI3K; Akt; mTOR signaling pathway; functional recovery
资金
- Beijing Excellent Talent Training Funding [2017000021469G215]
- Natural Science Foundation of Capital Medical University of China [PYZ2017082, PYZ2018081]
- China Rehabilitation Research Center Foundation [2018zx-Q3]
IGF-1 promotes functional recovery in rats following SCI through activation of the PI3K/Akt/mTOR signaling pathway and inhibition of autophagy. Positive therapeutic effects were observed in both cell and animal experiments.
Spinal cord injury (SCI) is a serious trauma; however, the mechanisms underlying the role of insulin-like growth factor 1 (IGF-1) in autophagy following SCI remain to be elucidated. The present study aimed to investigate the therapeutic effect of IGF-1 on SCI and to determine whether IGF-1 regulates autophagy via the PI3K/Akt/mTOR signaling pathway. SH-SY5Y neuroblastoma cells were assigned to the H2O2, IGF-1 and control groups to investigate subsequent neuron injury in vitro. An MTT assay was performed to evaluate cell survival. In addition, Sprague-Dawley rats were randomly assigned to SCI, SCI + IGF-1 and sham groups, and Basso-Beatlie-Bresnahan scores were assessed to determine rat neurological function. Western blotting was used to analyze the autophagy level and the activation of the PI3K/Akt/mTOR signaling pathway. Cell survival was increased significantly in the IGF-1 group compared with the control group in vitro (P<0.05). Furthermore, neurological function was improved in the SCI + IGF-1 group compared with the control group in vivo (P<0.05). The western blotting results further demonstrated that LC3II/LC3I expression was increased in the IGF-1 group compared with the sham group in vivo and compared with the control group in vitro (both P<0.05). In the SCI + IGF-1 group, the expression levels of PI3K, phosphorylated (p)-Akt and p-mTOR were higher compared with those in the sham and SCI groups in vivo (P<0.05). Moreover, in the IGF-1 group, the expression levels of p-Akt and p-mTOR were higher compared with the control and the H2O2 groups in vitro (P<0.05). Collectively, the results of the present study suggested that IGF-1 promoted functional recovery in rats following SCI through neuroprotective effects. Furthermore, the underlying mechanism may involve activation of the PI3K/Akt/mTOR signaling pathway, followed by inhibition of autophagy. However, further investigation into the association between IGF-1-regulated autophagy and the activation of different subtypes of PI3K is required.
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