Institute of Neuroscience, Chongqing Medical University, Chongqing, China.
Central Blood Bank, Sichuan Cancer Hospital and Research Institute, Chengdu, China.
Brain Res. 2019 Oct 15;1721:146347. doi: 10.1016/j.brainres.2019.146347. Epub 2019 Jul 23.
We previously reported that aquaporin 4 (AQP4) played a critical role in formation of brain edema and the altered expression of dystroglycan (DG) could relate with AQP4 expression after traumatic brain injury (TBI). However the mechanisms of this process remain unclear. DG was showed could act as a scaffold involved in adhesion-mediated signaling in ERK/MAPK pathway. We hypothesize that after scratch, extracellular α-DG and transmembrane β-DG may act as the scaffold in scratch mechanical force activating ERK pathway which may regulate the expression of AQP4. Use ERK inhibitor and activator to confirm whether the expression of AQP4 is regulated by the activation of ERK pathway in scratched astrocytes. Use DG siRNA to confirm whether DG takes part in the process that the extracellular signal transduces into cell and activates the ERK pathway. The significant increase of AQP4 and DG expression induced by scratch could be abolished by blocking ERK signaling and enhanced by activating ERK signaling. Blockade of DG by siRNA led to no obvious effect of scratched-injury on the ERK signaling pathway. It demonstrated that DG may act as the scaffold in scratch mechanical force activating ERK pathway which can regulate the expression of AQP4 in astrocytes after scratch.
我们之前的报告表明，水通道蛋白 4（AQP4）在脑水肿的形成中起关键作用，而营养不良性脑糖蛋白（DG）的表达改变可能与创伤性脑损伤（TBI）后 AQP4 的表达有关。然而，这一过程的机制尚不清楚。DG 可以作为细胞内 ERK/MAPK 信号通路中涉及黏附介导信号的支架。我们假设，在划痕后，细胞外的α-DG 和跨膜的β-DG 可能作为支架激活 ERK 通路，从而调节 AQP4 的表达。使用 ERK 抑制剂和激活剂来确定划痕机械力激活 ERK 通路是否可以调节划痕星形胶质细胞中 AQP4 的表达。使用 DG siRNA 来确定 DG 是否参与细胞外信号转导并激活 ERK 通路的过程。阻断 ERK 信号可以消除划痕诱导的 AQP4 和 DG 表达的显著增加，而激活 ERK 信号则增强了这种增加。用 siRNA 阻断 DG 对划痕损伤诱导的 ERK 信号通路没有明显影响。这表明，DG 可能作为划痕机械力激活 ERK 通路的支架，从而调节划痕后星形胶质细胞中 AQP4 的表达。
