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IGF-1 Combined with OPN Promotes Neuronal Axon Growth in Vitro Through the IGF-1R/Akt/mTOR Signaling Pathway in Lipid Rafts

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Abstract

This study aims to investigate the effect of insulin-like growth factor 1 (IGF-1) combined with osteopontin (OPN) on the protein expression levels and growth of neuronal axons and its possible mechanism. In this study, IGF-1 combined with OPN promoted neuronal axon growth through the IGF-1R/Akt/mTOR signaling pathway in lipid rafts, and the effect was better than that of either agent alone. This effect was suppressed when given the mTOR inhibitor rapamycin or the lipid raft cholesterol extraction agent methyl-β-cyclodextrin (M-β-CD). Rapamycin could inhibit the expression of phosphorylated ribosomal S6 protein (p-S6) and phosphorylated protein kinase B (p-Akt) and limit axon growth. In addition to the above effects, M-β-CD significantly downregulated the expression of phosphorylated insulin-like growth factor 1 receptor (p-IR). To further investigate the changes in lipid rafts when stimulated by different recombinant proteins, membrane lipid rafts were isolated to observe the changes by western blot. The expression levels of insulin-like growth factor 1 receptor (IR) and P-IR in the IGF-1 combined with OPN group were the highest. When M-β-CD was administered to the lipid rafts of neurons, the enrichment of IR by IGF-1 combined with OPN was weakened, and the p-IR was decreased. Our study found that IGF-1 combined with OPN could promote axon growth by activating the IGF-1R/Akt/mTOR signaling pathway in neuronal lipid rafts.

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Acknowledgements

The authors sincerely appreciate the experimental platform support of the State Key Laboratory of Trauma, Burns and Combined Injury, Department of Research Institute of Surgery, Daping Hospital, Army Military Medical University.

Funding

Botao Tan, Wei Jiang and Ying Yin have acquired the rewards of the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University. This work was supported in part by the National Natural Science Foundation of China (82002377) and Natural Science Foundation of Chongqing (cstc2020jcyj-msxm0651).

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Authors and Affiliations

  1. Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

    Qin Zhao, Hong Su, Wei Jiang, Haodong Luo, Lu Pan, Ying Yin, Lehua Yu & Botao Tan

  2. State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China

    Yuan Liu & Ce Yang

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Qin Zhao wrote the main manuscript text; Hong Su and Wei Jiang performed the data analyses; Haodong Luo and Lu Pan prepared figures; Lehua Yu and Botao Tan reviewed, revised the manuscript. All authors reviewed the manuscript.

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Zhao, Q., Su, H., Jiang, W. et al. IGF-1 Combined with OPN Promotes Neuronal Axon Growth in Vitro Through the IGF-1R/Akt/mTOR Signaling Pathway in Lipid Rafts. Neurochem Res 48, 3190–3201 (2023). https://doi.org/10.1007/s11064-023-03971-3

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