title: Peripheral nerve regeneration and NGF-dependent neurite outgrowth of adult sensory neurons converge on STAT3 phosphorylation downstream of neuropoietic cytokine receptor gp130.
abstract: After nerve injury, adult sensory neurons can regenerate peripheral axons and reconnect with their target tissue. Initiation of outgrowth, as well as elongation of neurites over long distances, depends on the signaling of receptors for neurotrophic growth factors. Here, we investigated the importance of gp130, the signaling subunit of neuropoietic cytokine receptors in peripheral nerve regeneration. After sciatic nerve crush, functional recovery in vivo was retarded in SNS-gp130(-/-) mice, which specifically lack gp130 in sensory neurons. Correspondingly, a significantly reduced number of free nerve endings was detected in glabrous skin from SNS-gp130(-/-) compared with control mice after nerve crush. Neurite outgrowth and STAT3 activation in vitro were severely reduced in cultures in gp130-deficient cultured neurons. Surprisingly, in neurons obtained from SNS-gp130(-/-) mice the increase in neurite length was reduced not only in response to neuropoietic cytokine ligands of gp130 but also to nerve growth factor (NGF), which does not bind to gp130-containing receptors. Neurite outgrowth in the absence of neurotrophic factors was partially rescued in gp130-deficient neurons by leptin, which activates STAT3 downstream of leptic receptor and independent of gp130. The neurite outgrowth response of gp130-deficient neurons to NGF was fully restored in the presence of leptin. Based on these findings, gp130 signaling via STAT3 activation is suggested not only to be an important regulator of peripheral nerve regeneration in vitro and in vivo, but as determining factor for the growth promoting action of NGF in adult sensory neurons.
authors.affiliation: Divisions of Physiology, and.
authors.forename: Serena
authors.initials: S
authors.lastname: Quarta
authors.affiliation: Neurobiochemistry, and.
authors.forename: Bastian E
authors.initials: BE
authors.lastname: Baeumer
authors.affiliation: Divisions of Physiology, and Centre for Stroke Research Berlin, Charite-Universitätsmedizin, Campus Virchow, D-10117 Berlin, Germany, and.
authors.forename: Nadja
authors.initials: N
authors.lastname: Scherbakov
authors.affiliation: Divisions of Physiology, and.
authors.forename: Manfred
authors.initials: M
authors.lastname: Andratsch
authors.affiliation: Department of Biochemistry, Christian-Albrechts-University, D-24098 Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
authors.affiliation: Institute of Neuroscience, Medical University Innsbruck, A-6020, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Dechant
authors.affiliation: Neurobiochemistry, and.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Bandtlow
authors.affiliation: Divisions of Physiology, and michaela.kress@i-med.ac.at.
authors.forename: Michaela
authors.initials: M
authors.lastname: Kress
mesh_terms: D000818:Animals; D048708:Cell Growth Processes; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000378:metabolism*; D020738:Leptin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000494:pharmacology; D009416:Nerve Regeneration; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D012584:Sciatic Nerve / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
chemical_list: C494200:Il6st protein, mouse; D020738:Leptin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D050822:Cytokine Receptor gp130; D020932:Nerve Growth Factor
keywords: NGF; PNS; STAT3; cytokines; gp130; regeneration