Abstract
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 study we demonstrated that pre-treatment of NPCs with PDGF-BB restored Tat-mediated impairment of cell proliferation via activation of p38 and JNK MAPK pathways. Moreover, treatment with PDGF-BB induced inactivation of glycogen synthase kinase-3β (GSK-3β), evidenced by its phosphorylation at Ser9, this effect was significantly inhibited by the p38 and JNK inhibitors. Level of nuclear β-catenin, the primary substrate of GSK-3β, was also concomitantly increased following PDGF-BB treatment, suggesting that PDGF-BB stimulates NPC proliferation via acting on GSK-3β to promote nuclear accumulation of β-catenin. This was further validated by gain and loss of function studies using cells transfected with either the wild type or mutant GSK-3β constructs. Together these data underpin the role of GSK-3β/β-catenin as a novel target that regulates NPC proliferation mediated by PDGF-BB with implications for therapeutic intervention for reversal of impaired neurogenesis inflicted by Tat.
Original language | English (US) |
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Pages (from-to) | 259-268 |
Number of pages | 10 |
Journal | Journal of Neuroimmune Pharmacology |
Volume | 9 |
Issue number | 2 |
DOIs | |
State | Published - Mar 2014 |
Keywords
- Beta-catenin
- GSK-3 beta
- HIV Tat
- Neuronal progenitor cell
- PDGF-BB
ASJC Scopus subject areas
- Neuroscience (miscellaneous)
- Immunology and Allergy
- Immunology
- Pharmacology