PDF(Pubmed)
Abstract：
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.
摘要：
周围神经胶质雪旺细胞在神经损伤后切换到修复状态，增殖以提供丢失的细胞群，迁移形成再生轨迹，并有助于产生神经再生的允许微环境。探索雪旺氏细胞修复反应的基本调节因子可能有利于周围神经损伤的临床治疗。在本研究中,我们发现，编码转录因子FOS样1的AP-1成员FOSL1在周围神经挤压后的损伤部位高度表达。干扰FOSL1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。总的来说，我们的研究结果揭示了FOSL1在调节雪旺氏细胞活化中的重要作用,并表明FOSL1可以作为一种新的治疗方法来协调受损周围神经的再生和功能恢复.
