中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (1): 166-171.doi: 10.4103/1673-5374.286978

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

敲除Krüppel样因子4基因可促进哺乳动物轴突再生?

  

  • 出版日期:2021-01-15 发布日期:2020-11-26
  • 基金资助:
    国家自然科学基金项目(81571189,81772353)

Deletion of Krüppel-like factor-4 promotes axonal regeneration in mammals

Jin-Hui Xu, Xu-Zhen Qin, Hao-Nan Zhang, Yan-Xia Ma, Shi-Bin Qi, Hong-Cheng Zhang, Jin-Jin Ma, Xin-Ya Fu, Ji-Le Xie, Saijilafu*#br#   

  1. Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, Jiangsu Province, China
  • Online:2021-01-15 Published:2020-11-26
  • Contact: Saijilafu, MD, PhD, saijilafu@suda.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81571189, 81772353 (to Saijilafu).

摘要:

轴突再生在神经系统受损后的功能恢复中起着重要的作用,但是哺乳动物轴突一旦损伤后,其再生能力通常较差。Krüppel样因子4敲除可促进视网膜神经节细胞中轴突的再生,但是其对皮质脊髓束和周围神经系统的影响尚不清楚。为此,实验首先建立坐骨神经损伤成年小鼠模型,发现其Krüppel样因子4的表达降低,因此考虑小鼠坐骨神经的再生可能和Krüppel样因子4相关;接着对敲除Krüppel样因子4基因的视网膜神经节感觉神经元进行体外培养,发现神经元轴突的再生能力明显增强;然后对视网膜神经节感觉神经元敲除了Klf4基因的小鼠建立坐骨神经夹伤模型,发现体内实验中坐骨神经的再生能力也增强了;最后以AAV-Cre病毒转染敲除小鼠大脑皮质中的Krüppel样因子4基因,发现脊髓损伤的小鼠皮质脊髓束的再生能力同样增强;因此,作者认为调控神经元Krüppel样因子4基因表达可能成为一种促进神经系统损伤后轴突再生和功能恢复的潜在方法。实验经苏州大学动物伦理委员会批准。

https://orcid.org/0000-0003-2290-9808 (Saijilafu) 

关键词: Krüppel样因子4基因, 皮质脊髓束, 周围神经, 轴突再生, 背根神经节, 感觉运动皮质, 坐骨神经挤压伤, 脊髓挤压损伤

Abstract: Axonal regeneration plays an important role in functional recovery after nervous system damage. However, after axonal injury in mammals, regeneration is often poor. The deletion of Krüppel-like factor-4 (Klf4) has been shown to promote axonal regeneration in retinal ganglion cells. However, the effects of Klf4 deletion on the corticospinal tract and peripheral nervous system are unknown. In this study, using a mouse model of sciatic nerve injury, we show that the expression of Klf4 in dorsal root ganglion sensory neurons was significantly reduced after peripheral axotomy, suggesting that the regeneration of the sciatic nerve is associated with Klf4. In vitro, dorsal root ganglion sensory neurons with Klf4 knockout exhibited significantly enhanced axonal regeneration. Furthermore, the regeneration of the sciatic nerve was enhanced in vivo following Klf4 knockout. Finally, AAV-Cre virus was used to knockout the Klf4 gene in the cortex. The deletion of Klf4 enhanced regeneration of the corticospinal tract in mice with spinal cord injury. Together, our findings suggest that regulating KLF4 activity in neurons is a potential strategy for promoting axonal regeneration and functional recovery after nervous system injury. This study was approved by the Animal Ethics Committee at Soochow University, China (approval No. SUDA20200316A01).

Key words: axonal regeneration, corticospinal tract, dorsal root ganglion, Klf4, peripheral nervous system, sciatic nerve crush, sensorimotor cortex, spinal cord crushl