Neuron and microglia/macrophage-derived FGF10 activate neuronal FGFR2/PI3K/Akt signaling and inhibit microglia/macrophages TLR4/NF-κB-dependent neuroinflammation to improve functional recovery after spinal cord injury

作者：Chen, Jian; Wang, Zhouguang; Zheng, ZengMing; Chen, Yu; Khor, Sinan; Shi, KeSi; He, ZiLi; Wang, Qingqing; Zhao, Yingzheng; Zhang, Hongyu; Li, Xiaokun; Li, Jiawei; Yin, Jiayu; Wang, Xiangyang^*; Xiao, Jian^*

来源：Cell Death & Disease, 2017, 8(10): e3090.

DOI：10.1038/cddis.2017.490

• FOCAL CEREBRAL-ISCHEMIA
• MICROTUBULE-ASSOCIATED PROTEIN-2
• BLOOD-BRAIN-BARRIER
• AXON REGENERATION
• ISCHEMIA/REPERFUSION INJURY
• SUBARACHNOID HEMORRHAGE
• SECONDARY DAMAGE
• OXIDATIVE STRESS
• CYTOCHROME-C
• CELL-DEATH

Therapeutics used to treat central nervous system (CNS) injury were designed to repair neurites and inhibit cell apoptosis. Previous studies have shown that neuron-derived FGF10 exerts potential neuroprotective effects after cerebral ischemia injury. However, little is known about the role of endogenous FGF10 in the recovery process after spinal cord injury (SCI). In this study, we found that FGF10 is mainly produced by neuron and microglia/macrophages, and its expression is increased after SCI. Exogenous treatment of FGF10 improved functional recovery after injury by reducing apoptosis, as well as repairing neurites via FGFR2/PI3K/Akt pathway. On another hand, inhibiting the PI3K/Akt pathway with LY294002 partially reversed the therapeutic effects of FGF10. In addition, small interfering RNA knockdown of FGFR2 suppressed PI3K/Akt pathway activation by FGF10 and abolished its anti-apoptotic and neurite repair effects in vitro. Furthermore, FGF10 treatment inhibited the activation and proliferation of microglia/macrophages through regulation of TLR4/NF-kappa B pathway, and attenuated the release of pro-inflammatory cytokines after SCI. Thus, the increased expression of FGF10 after acute SCI is an endogenous self-protective response, suggesting that FGF10 could be a potential treatment for CNS injury.

• 出版日期2017-10
• 单位温州医科大学