Dystroglycan is involved in the activation of ERK pathway inducing the change of AQP4 expression in scratch-injured astrocytes

Abstract

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.