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Nerve injury induces glial cell line‐derived neurotrophic factor (gdnf) expression in schwann cells through purinergic signaling and the pkc‐pkd pathway
Author(s) -
Xu Pin,
Rosen Kenneth M.,
Hedstrom Kristian,
Rey Osvaldo,
Guha Sushovan,
Hart Courtney,
Corfas Gabriel
Publication year - 2013
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22491
Subject(s) - glial cell line derived neurotrophic factor , gdnf family of ligands , neurotrophic factors , schwann cell , microbiology and biotechnology , biology , downregulation and upregulation , purinergic receptor , neuroscience , nerve injury , proto oncogene proteins c ret , signal transduction , peripheral nerve injury , receptor , regeneration (biology) , biochemistry , extracellular , gene
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.