title: Expression of CNTF/LIF-receptor components and activation of STAT3 signaling in axotomized facial motoneurons: evidence for a sequential postlesional function of the cytokines.
abstract: Several lines of evidence suggest that ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) are important for the survival and regeneration of axotomized motoneurons. To investigate the role of CNTF/LIF signaling in regenerative responses of motoneurons, we studied the expression of the three receptor components, CNTF receptor alpha (CNTFRalpha), LIF receptor beta (LIFRbeta), and gp130, and the activation of the STAT3 signal transduction pathway in the rat facial nucleus following peripheral nerve transection. As shown by in situ hybridization and immunoblotting, axotomy resulted in a rapid down-regulation of CNTFRalpha mRNA expression within 24 h and a concomitant massive up-regulation of LIFRbeta mRNA and protein in the lesioned motoneurons. The altered mRNA levels were maintained for 3 weeks but had returned back to control levels by 6 weeks postlesion after successful regeneration. In contrast, mRNA levels remained in the lesioned state during the 6-week period studied, when regeneration was prevented by nerve resection. Significant lesion-induced changes in gp130 mRNA levels were not detectable. Rapid (within 24 h) and sustained (for at least 5 days) activation of STAT3 in axotomized facial motoneurons was revealed by demonstrating the phosphorylation and nuclear translocation of the protein using immunocytochemistry and immunoblotting. In agreement with previous studies showing a complementary regulation of CNTF and LIF in the lesioned facial nerve, our observations on the postlesional regulation of CNTF/LIF receptor components in the facial nucleus indicate a direct and sequential action of the two neurotrophic proteins on axotomized facial motoneurons.
authors.affiliation: Institute of Anatomy, University of Freiburg, P.O. Box 111, D-79001 Freiburg, Germany.
authors.forename: C A
authors.initials: CA
authors.lastname: Haas
authors.forename: H D
authors.initials: HD
authors.lastname: Hofmann
authors.forename: M
authors.initials: M
authors.lastname: Kirsch
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics; D000818:Animals; D019771:Axotomy; D001483:Base Sequence; D058966:Contactins; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005154:Facial Nerve / Q000502:physiology*; D005786:Gene Expression Regulation; D006131:Growth Inhibitors; D017403:In Situ Hybridization; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; D008297:Male; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000502:physiology*; D009416:Nerve Regeneration; D019006:Neural Cell Adhesion Molecules / Q000235:genetics; D010525:Peripheral Nerves / Q000502:physiology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020801:Receptor, Ciliary Neurotrophic Factor / Q000235:genetics*; D018121:Receptors, Cytokine / Q000235:genetics*; D053606:Receptors, OSM-LIF; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000209:Acute-Phase Proteins; D058966:Contactins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507842:Lifr protein, rat; D008222:Lymphokines; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators