Platelet-Derived Growth Factor-BB Restores HIV Tat -Mediated Impairment of Neurogenesis: Role of GSK-3β/β-Catenin

摘要: Our previous study demonstrated that platelet-derived growth factor-BB (PDGF-BB) increased the cell proliferation of primary rat neuronal progenitor cells (NPCs). However, whether PDGF-BB regulates neurogenesis in HIV-associated neurological disorder (HAND) remains largely unknown. In this we pre-treatment NPCs with restored Tat-mediated impairment via activation p38 and JNK MAPK pathways. Moreover, treatment induced inactivation glycogen synthase kinase-3β (GSK-3β), evidenced by its phosphorylation at Ser9, effect was significantly inhibited inhibitors. Level nuclear β-catenin, substrate GSK-3β, also concomitantly following treatment, suggesting stimulates NPC acting on GSK-3β to promote accumulation β-catenin. This further validated gain loss function studies using transfected either wild type or mutant constructs. Together these data underpin role GSK-3β/β-catenin as a novel target mediated implications for therapeutic intervention reversal impaired inflicted Tat.