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

作者全名："Zhao, Qin; Su, Hong; Jiang, Wei; Luo, Haodong; Pan, Lu; Liu, Yuan; Yang, Ce; Yin, Ying; Yu, Lehua; Tan, Botao"

作者地址："[Zhao, Qin; Su, Hong; Jiang, Wei; Luo, Haodong; Pan, Lu; Yin, Ying; Yu, Lehua; Tan, Botao] Chongqing Med Univ, Dept Rehabil Med, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Liu, Yuan; Yang, Ce] Army Med Univ, Daping Hosp, Res Inst Surg, State Key Lab Trauma Burn & Combined Injury, Chongqing, Peoples R China"

通信作者："Yu, LH; Tan, BT (通讯作者)，Chongqing Med Univ, Dept Rehabil Med, Affiliated Hosp 2, Chongqing 400010, Peoples R China."

来源：NEUROCHEMICAL RESEARCH

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001022798700001

JCR分区：Q2

影响因子：3.7

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Cortical neurons; IGF-1; OPN; IGF-1R/Akt/mTOR signaling pathway; Lipid rafts; M-beta-CD

摘要："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-beta-cyclodextrin (M-beta-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-beta-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-beta-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."

基金机构：National Natural Science Foundation of China [82002377]; Natural Science Foundation of Chongqing [cstc2020jcyj-msxm0651]

基金资助正文："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)."