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

30 Citations (Scopus)

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 2013

Fingerprint

Glial Cell Line-Derived Neurotrophic Factor
Schwann Cells
Peripheral Nerve Injuries
Nerve Growth Factors
Wounds and Injuries
Up-Regulation
Purinergic Receptors
Peripheral Nervous System Diseases
Neuroglia
Protein Kinase C
Regeneration
Neurons
protein kinase D

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Nerve injury induces glial cell line-derived neurotrophic factor (GDNF) expression in schwann cells through purinergic signaling and the PKC-PKD pathway. / Xu, Pin; Rosen, Kenneth M.; Hedstrom, Kristian; Rey, Osvaldo; Guha, Sushovan; Hart, Courtney; Corfas, Gabriel.

In: GLIA, Vol. 61, No. 7, 07.2013, p. 1029-1040.

Research output: Contribution to journalArticle

Xu, Pin ; Rosen, Kenneth M. ; Hedstrom, Kristian ; Rey, Osvaldo ; Guha, Sushovan ; Hart, Courtney ; Corfas, Gabriel. / Nerve injury induces glial cell line-derived neurotrophic factor (GDNF) expression in schwann cells through purinergic signaling and the PKC-PKD pathway. In: GLIA. 2013 ; Vol. 61, No. 7. pp. 1029-1040.
@article{f7ef080d5a6048bda0118d3b5060b8be,
title = "Nerve injury induces glial cell line-derived neurotrophic factor (GDNF) expression in schwann cells through purinergic signaling and the PKC-PKD pathway",
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.",
keywords = "Apyrase, GDNF, Nerve injury, Protein kinase D, Purinergic receptor, Schwann cell",
author = "Pin Xu and Rosen, {Kenneth M.} and Kristian Hedstrom and Osvaldo Rey and Sushovan Guha and Courtney Hart and Gabriel Corfas",
year = "2013",
month = "7",
doi = "10.1002/glia.22491",
language = "English (US)",
volume = "61",
pages = "1029--1040",
journal = "GLIA",
issn = "0894-1491",
publisher = "John Wiley and Sons Inc.",
number = "7",

}

TY - JOUR

T1 - Nerve injury induces glial cell line-derived neurotrophic factor (GDNF) expression in schwann cells through purinergic signaling and the PKC-PKD pathway

AU - Xu, Pin

AU - Rosen, Kenneth M.

AU - Hedstrom, Kristian

AU - Rey, Osvaldo

AU - Guha, Sushovan

AU - Hart, Courtney

AU - Corfas, Gabriel

PY - 2013/7

Y1 - 2013/7

N2 - 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.

AB - 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.

KW - Apyrase

KW - GDNF

KW - Nerve injury

KW - Protein kinase D

KW - Purinergic receptor

KW - Schwann cell

UR - http://www.scopus.com/inward/record.url?scp=84879600891&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879600891&partnerID=8YFLogxK

U2 - 10.1002/glia.22491

DO - 10.1002/glia.22491

M3 - Article

VL - 61

SP - 1029

EP - 1040

JO - GLIA

JF - GLIA

SN - 0894-1491

IS - 7

ER -