Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Oxid Med Cell Longev. 2022 Mar 16;2022:7474177. doi: 10.1155/2022/7474177. eCollection 2022.
Spinal cord injury (SCI) is a severe traumatic condition. The loss of the bundle of axons involved in motor conduction in the spinal cord after SCI is the main cause of motor function injury. Presently, axon regeneration in the spinal cord has been studied extensively, but it remains unclear how axon growth is regulated in an inflammatory environment at the cellular level. In the present study, GIT1 knockout (KO) mouse neurons were cultured in a microfluidic device to simulate the growth of axons in an inflammatory environment. The molecular regulation of axon growth in an inflammatory environment by GIT1 was then investigated. We found that the axon growth of GIT1 KO mouse neurons was restricted in an inflammatory environment. Further investigations revealed that in both axons and cell bodies in the inflammatory environment, GIT1 phosphorylated ERK, promoted the entry of Nrf2 into the nucleus, and promoted the transcription of MAP1B, thereby increasing the levels of MAP1B and p-MAP1B and promoting axon growth. We also found that MAP1B could be translated locally in axons and transported in cell bodies and axons. In conclusion, we found that GIT1 regulated axon growth in an inflammatory environment. This provided a theoretical basis for axon regeneration in an inflammatory environment after SCI to develop new treatment options for axon regeneration.
脊髓损伤 (SCI) 是一种严重的创伤性疾病。SCI 后脊髓中参与运动传导的轴突束的丢失是运动功能损伤的主要原因。目前，脊髓中的轴突再生已经得到了广泛的研究，但在细胞水平上，轴突生长在炎症环境中是如何被调控的仍不清楚。在本研究中，我们使用微流控装置培养 GIT1 敲除 (KO) 小鼠神经元，以模拟炎症环境中轴突的生长。然后，我们研究了 GIT1 在炎症环境中对轴突生长的分子调控作用。我们发现，GIT1 KO 小鼠神经元的轴突生长在炎症环境中受到限制。进一步的研究表明，在炎症环境中的轴突和细胞体中，GIT1 磷酸化 ERK，促进 Nrf2 进入细胞核，并促进 MAP1B 的转录，从而增加 MAP1B 和 p-MAP1B 的水平，促进轴突生长。我们还发现，MAP1B 可以在轴突中局部翻译，并在细胞体和轴突中运输。总之，我们发现 GIT1 调控了炎症环境中的轴突生长。这为 SCI 后炎症环境中的轴突再生提供了理论基础，为开发新的轴突再生治疗方法提供了依据。
