Platelet-derived growth factor-BB restores HIV Tat-mediated impairment of neurogenesis: Role of GSK-3β/β-catenin

Jie Chao, Lu Yang, Honghong Yao, Shilpa Buch

Research output: Contribution to journalArticle

18 Scopus citations

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 languageEnglish (US)
Pages (from-to)259-268
Number of pages10
JournalJournal of Neuroimmune Pharmacology
Volume9
Issue number2
DOIs
StatePublished - 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

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