title: Nerve injury-induced c-Jun activation in Schwann cells is JNK independent.
abstract: We investigated (a) if activation of the mitogen activated protein kinase (MAPK) pathway was linked to the stress activated protein kinase (SAPK) pathway and (b) if JNK was required for activation of c-Jun in Schwann cells of rat sciatic nerve following injury. To this aim, ERK1/2 and the transcription factors c-Jun and ATF-3 were studied by immunohistochemistry in segments of transected nerves. We utilized pharmacological inhibitors of both signal transduction pathways in vitro to determine the effects on downstream signalling events, such as c-Jun activation, and on Schwann cell survival and proliferation. A transection induces c-Jun and ATF-3 transcription in Schwann cells. These events are followed by Schwann cell activation of c-Jun in the injured nerve. The MAPK inhibitor U0126 blocked ERK1/2 activation and reduced Schwann cell proliferation as well as induction of c-Jun transcription. The JNK inhibitor SP600125 reduced Schwann cell proliferation, but did not affect the expression of ERK1/2 or injury-induced increases in c-Jun or ATF-3 levels. Importantly, nerve injury induces Schwann cell activation of c-Jun by phosphorylation, which, in contrast to in sensory neurons, is JNK independent. MAP kinases, other than JNK, can potentially activate c-Jun in Schwann cells following injury; information that is crucial to create new nerve reconstruction strategies.
authors.affiliation: Cellectricon AB, Flöjelbergsgatan 8C, 431 37 Mölndal, Sweden.
authors.forename: Charlotta Lindwall
authors.initials: CL
authors.lastname: Blom
authors.affiliation: Department of Biology/Functional Zoology, Lund University, Sölvegatan 35, 223 62 Lund, Sweden.
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Mårtensson
authors.affiliation: Department of Clinical Sciences in Malmö/Hand Surgery, Lund University, Skåne University Hospital, Jan Waldenströms Gata 5, 205 02 Malmö, Sweden.
authors.forename: Lars B
authors.initials: LB
authors.lastname: Dahlin
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D005260:Female; D048670:MAP Kinase Kinase 4; D020935:MAP Kinase Signaling System; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic
chemical_list: D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D016755:Proto-Oncogene Proteins c-jun; D048052:Mitogen-Activated Protein Kinase 3; D048670:MAP Kinase Kinase 4