Nerve injury induces glial cell line-derived neurotrophic factor (GDNF) expression in schwann cells through purinergic signaling and the PKC-PKD pathway

Pin Xu, Kenneth M. Rosen, Kristian Hedstrom, Osvaldo Rey, Sushovan Guha, Courtney Hart, Gabriel Corfas

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Upon peripheral nerve injury, specific molecular events, including increases in the expression of selected neurotrophic factors, are initiated to prepare the tissue for regeneration. However, the mechanisms underlying these events and the nature of the cells involved are poorly understood. We used the injury-induced upregulation of glial cell-derived neurotrophic factor (GDNF) expression as a tool to gain insights into these processes. We found that both myelinating and nonmyelinating Schwann cells are responsible for the dramatic increase in GDNF expression after injury. We also demonstrate that the GDNF upregulation is mediated by a signaling cascade involving activation of Schwann cell purinergic receptors, followed by protein kinase C signaling which activates protein kinase D (PKD), which leads to increased GDNF transcription. Given the potent effects of GDNF on survival and repair of injured peripheral neurons, we propose that targeting these pathways may yield therapeutic tools to treat peripheral nerve injury and neuropathies.

Original languageEnglish (US)
Pages (from-to)1029-1040
Number of pages12
JournalGLIA
Volume61
Issue number7
DOIs
StatePublished - Jul 1 2013

Keywords

  • Apyrase
  • GDNF
  • Nerve injury
  • Protein kinase D
  • Purinergic receptor
  • Schwann cell

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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