Department of Orthopedic, Liaoning University of Traditional Chinese Medicine, Shenyang, People's Republic of China.
Department of Stomatology, Second Affiliated Hospital of Jinzhou Medical University, Jinzhou, People's Republic of China.
Neurochem Res. 2018 Jul;43(7):1405-1412. doi: 10.1007/s11064-018-2555-2. Epub 2018 May 22.
Wnt signaling are recognized key factors in neuronal development, cell proliferation and axonal guidance. However, RAGE effect on wnt signaling after spinal cord injury (SCI) are poorly understood. Our study aims to explore RAGE blockade effect on wnt signaling after SCI. We constructed Allen SCI model and micro-injected with RAGE neutralizing antibody or IgG after injury. We determined β-catenin, wnt3a and its receptor frizzled-5 via Western blot. We determined β-catenin/NeuN expression at 2 weeks after SCI via immunofluorescence (IF). We found that β-catenin, wnt3a and wnt receptor frizzled5 expression were activated after SCI at 3 days after injury. However, RAGE blockade inhibit β-catenin, wnt3a and frizzled5 expression. We found that β-catenin accumulation in NeuN cells were activated after SCI via IF, however, RAGE blockade reduced β-catenin and NeuN positive cells. RAGE blockade attenuated number of survived neurons and decreased area of spared white matter around the epicenter. RAGE signaling may involved in disrupting wnt signaling to aids neuronal recovery after SCI.
Wnt 信号被认为是神经元发育、细胞增殖和轴突导向的关键因素。然而，RAGE 对脊髓损伤 (SCI) 后 wnt 信号的影响知之甚少。本研究旨在探讨 RAGE 阻断对 SCI 后 wnt 信号的影响。我们构建了 Allen SCI 模型，并在损伤后微注射 RAGE 中和抗体或 IgG。通过 Western blot 测定β-连环蛋白、wnt3a 及其受体 frizzled-5。通过免疫荧光 (IF) 测定 SCI 后 2 周β-连环蛋白/NeuN 的表达。结果发现，SCI 后 3 天β-连环蛋白、wnt3a 和 wnt 受体 frizzled5 的表达被激活。然而，RAGE 阻断抑制β-连环蛋白、wnt3a 和 frizzled5 的表达。通过 IF 发现，SCI 后β-连环蛋白在 NeuN 细胞中的积累被激活，然而，RAGE 阻断减少了β-连环蛋白和 NeuN 阳性细胞。RAGE 阻断减少了存活神经元的数量，并减少了损伤中心周围白质的保留面积。RAGE 信号可能参与破坏 wnt 信号，以帮助 SCI 后神经元的恢复。
