Therapeutic Potential of Growth Hormone in Peripheral Nerve Injury: Enhancing Schwann Cell Proliferation and Migration Through IGF-1R-AKT and ERK Signaling Pathways.

IF 5.4 2区 医学 Q1 NEUROSCIENCES Glia Pub Date : 2024-11-28 DOI:10.1002/glia.24653
Jiaqian Chen, Tingcheng Zhang, Chaohu Wang, Peirong Niu, Liehao Huang, Rongrong Guo, Chengdong Wu, Huarong Zhang, Zhiyong Wu, Songtao Qi, Yi Liu
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Abstract

Peripheral nerve injury (PNI) represents a prevalent condition characterized by the demyelination of affected nerves. The challenge of remyelinating these nerves and achieving satisfactory functional recovery has long been a persistent issue. The specific contributions of growth hormone (GH) in the aftermath of PNI have remained ambiguous. Our investigations have demonstrated that GH not only enhances neurological function scores but also promotes remyelination within a three-week period. Further in vivo studies corroborated that GH facilitates nerve function improvement by mitigating neuronal apoptosis. In vitro, the ideal concentration of GH for exerting effects on Schwann cells (SCs) has been identified as 80 ng/mL. Subsequent research uncovered GH's profound impact on SCs proliferation, cell cycle progression, and migration. Through RNA sequencing and additional experiments, it was discovered that GH treatment elevates the phosphorylation levels of IGF-1R, AKT, and ERK. Moreover, the GH-induced proliferation and migration of SCs were significantly diminished by the inhibition of the IGF-1R pathway, achieved through pre-treatment with Linsitinib. The outcomes of this investigation suggest that GH can significantly enhance the proliferation and migration of SCs, presenting it as a viable option for PNI repair.

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生长激素在周围神经损伤中的治疗潜力:通过IGF-1R-AKT和ERK信号通路促进雪旺细胞增殖和迁移。
周围神经损伤(PNI)是一种以受影响神经脱髓鞘为特征的普遍疾病。长期以来,对这些神经的髓鞘再生和实现令人满意的功能恢复的挑战一直是一个持久的问题。生长激素(GH)在PNI后的具体贡献仍然不明确。我们的研究表明生长激素不仅能提高神经功能评分,还能在三周内促进髓鞘再生。进一步的体内研究证实生长激素通过减轻神经元凋亡促进神经功能改善。体外,生长激素对雪旺细胞(SCs)发挥作用的理想浓度已被确定为80 ng/mL。随后的研究揭示了生长激素对SCs增殖、细胞周期进展和迁移的深远影响。通过RNA测序和其他实验,发现生长激素治疗可提高IGF-1R、AKT和ERK的磷酸化水平。此外,通过Linsitinib预处理,通过抑制IGF-1R通路,gh诱导的SCs增殖和迁移显著减少。本研究结果表明,生长激素可以显著增强SCs的增殖和迁移,这表明它是修复PNI的可行选择。
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来源期刊
Glia
Glia 医学-神经科学
CiteScore
13.10
自引率
4.80%
发文量
162
审稿时长
3-8 weeks
期刊介绍: GLIA is a peer-reviewed journal, which publishes articles dealing with all aspects of glial structure and function. This includes all aspects of glial cell biology in health and disease.
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