Polarizedexpression Of Aquaporin-4 Is Regulated By ERK/MAPK Pathway Via Dystroglycan In Scratch-wound Astrocytes

ObjectiveThe present study aims to investigate whether DG is involved in the polarization of AQP4,whether the regulation for polarization of AQP4 is depended on the activation of ERK pathway and whether DG takes part in this signal transport to activate the ERK pathway under injured condition in vitro.MethodsThe in vitro injury model was mimicked with primary cultures of rat astrocytes subjected to scratch-injury.Using a combination of immunoflurescent and biochemical studies,the expressions of AQP4,DG,ERK and phosphorylated ERK(p-ERK)were analyzed in scratch-injured astrocytes.Then,the effect of ERK was further investigated using pharmacologic inhibitor(U0126)or activator(TPA).DG expression was inhibited by small interfering RNA(si RNA).ResultsWe found that injury led to a significant increase in AQP4 and DG expressions which could be abolished by blocking ERK signaling and enhanced by activating ERK signaling.Besides,direct blockade of DG by siRNA led to downregulation of AQP4 and p-ERK.ConclusionsAfter scratch injury,the outside mechanical force caused by scratch through the extracellular α-DG and transmembrane β-DG transported into astrocytes and activated ERK pathway to regulate the polarization of AQP4 expression.