Chen Qianqian, Zhang Lan, Zhang Fuchao, Yi Sheng
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu, China.
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu, China.
J Biol Chem. 2023 Dec;299(12):105444. doi: 10.1016/j.jbc.2023.105444. Epub 2023 Nov 8.
Peripheral glial Schwann cells switch to a repair state after nerve injury, proliferate to supply lost cell population, migrate to form regeneration tracks, and contribute to the generation of a permissive microenvironment for nerve regeneration. Exploring essential regulators of the repair responses of Schwann cells may benefit the clinical treatment for peripheral nerve injury. In the present study, we find that FOSL1, a AP-1 member that encodes transcription factor FOS Like 1, is highly expressed at the injured sites following peripheral nerve crush. Interfering FOSL1 decreases the proliferation rate and migration ability of Schwann cells, leading to impaired nerve regeneration. Mechanism investigations demonstrate that FOSL1 regulates Schwann cell proliferation and migration by directly binding to the promoter of EPH Receptor B2 (EPHB2) and promoting EPHB2 transcription. Collectively, our findings reveal the essential roles of FOSL1 in regulating the activation of Schwann cells and indicate that FOSL1 can be targeted as a novel therapeutic approach to orchestrate the regeneration and functional recovery of injured peripheral nerves.
周围神经胶质雪旺细胞在神经损伤后转变为修复状态，增殖以补充丢失的细胞群体，迁移以形成再生轨迹，并有助于为神经再生生成有利的微环境。探索雪旺细胞修复反应的关键调节因子可能有益于周围神经损伤的临床治疗。在本研究中，我们发现FOSL1（一种编码转录因子FOS样蛋白1的AP-1成员）在周围神经挤压后的损伤部位高度表达。干扰FOSL1会降低雪旺细胞的增殖率和迁移能力，导致神经再生受损。机制研究表明，FOSL1通过直接结合EPH受体B2（EPHB2）的启动子并促进EPHB2转录来调节雪旺细胞的增殖和迁移。总体而言，我们的研究结果揭示了FOSL1在调节雪旺细胞激活中的重要作用，并表明FOSL1可作为一种新的治疗靶点，以协调受损周围神经的再生和功能恢复。
