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

被引:0
作者
Chen, Jiaqian [1 ]
Zhang, Tingcheng [1 ]
Wang, Chaohu [1 ]
Niu, Peirong [1 ]
Huang, Liehao [1 ]
Guo, Rongrong [1 ]
Wu, Chengdong [1 ]
Zhang, Huarong [1 ]
Wu, Zhiyong [2 ]
Qi, Songtao [1 ]
Liu, Yi [1 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Inst Brain Dis, Dept Neurosurg, Guangzhou, Peoples R China
[2] Southern Med Univ, Coll Tradit Chinese Med, Guangzhou, Peoples R China
关键词
AKT/ERK pathway; growth hormone; IGF-1R; migration; proliferation; Schwann cell; MANAGEMENT;
D O I
10.1002/glia.24653
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:805 / 821
页数:17
相关论文
共 38 条
[1]   Growth Hormone (GH) Crosses the Blood-Brain Barrier (BBB) and Induces Neuroprotective Effects in the Embryonic Chicken Cerebellum after a Hypoxic Injury [J].
Baltazar-Lara, Rosario ;
Zenil, Janeth Mora ;
Carranza, Martha ;
Avila-Mendoza, Jose ;
Martinez-Moreno, Carlos G. ;
Aramburo, Carlos ;
Luna, Maricela .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2022, 23 (19)
[2]   Protective role of IGF-1 and GLP-1 signaling activation in neurological dysfunctions [J].
Bhalla, Sonalika ;
Mehan, Sidharth ;
Khan, Andleeb ;
Rehman, Muneeb U. .
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, 2022, 142
[3]   Neurotrophic and Neuroregenerative Effects of GH/IGF1 [J].
Bianchi, Vittorio Emanuele ;
Locatelli, Vittorio ;
Rizzi, Laura .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2017, 18 (11)
[4]   Growth hormone receptor modulators [J].
Birzniece, Vita ;
Sata, Akira ;
Ho, Ken Ky .
REVIEWS IN ENDOCRINE & METABOLIC DISORDERS, 2009, 10 (02) :145-156
[5]  
Burnett Mark G, 2004, Neurosurg Focus, V16, pE1, DOI 10.3171/foc.2004.16.5.2
[6]   Evaluation and management of peripheral nerve injury [J].
Campbell, William W. .
CLINICAL NEUROPHYSIOLOGY, 2008, 119 (09) :1951-1965
[7]   Growth hormone receptor immunoreactivity is increased in the subventricular zone of juvenile rat brain after focal ischemia: A potential role for growth hormone in injury-induced neurogenesis [J].
Christophidis, Larissa Joy ;
Gorba, Thorsten ;
Gustavsson, Malin ;
Williams, Chris Edward ;
Werther, George Arthur ;
Russo, Vincenzo Carlo ;
Scheepens, Arjan .
GROWTH HORMONE & IGF RESEARCH, 2009, 19 (06) :497-506
[8]   Myelin debris regulates inflammatory responses in an experimental demyelination animal model and multiple sclerosis lesions [J].
Clarner, Tim ;
Diederichs, Felix ;
Berger, Katharina ;
Denecke, Bernd ;
Gan, Lin ;
Van der Valk, Paul ;
Beyer, Cordian ;
Amor, Sandra ;
Kipp, Markus .
GLIA, 2012, 60 (10) :1468-1480
[9]   Multiple Effects of Growth Hormone in the Body: Is it Really the Hormone for Growth? [J].
Devesa, Jesus ;
Almenglo, Cristina ;
Devesa, Pablo .
CLINICAL MEDICINE INSIGHTS-ENDOCRINOLOGY AND DIABETES, 2016, 9 :47-71
[10]   Growth hormone reverses streptozotocin-induced cognitive impairments in male mice [J].
Enhamre-Brolin, Erika ;
Carlsson, Anna ;
Hallberg, Mathias ;
Nyberg, Fred .
BEHAVIOURAL BRAIN RESEARCH, 2013, 238 :273-278