Ciliary neurotrophic factor activates JAK/Stat signal transduction cascade and induces transcriptional expression of glial fibrillary acidic protein in glial cells

J Neurochem. 1997 Apr;68(4):1413-23. doi: 10.1046/j.1471-4159.1997.68041413.x.


In recent reports, ciliary neurotrophic factor (CNTF) has been implicated as an injury factor involved in regulating astrogliosis in the CNS. In this study, we used a rat oligodendroglial progenitor cell line that is highly responsive to CNTF to examine CNTF-induced alterations that may play a role in activation of the glial fibrillary acidic protein (GFAP) gene. We determined that CNTF induces the transient translocation of Stat1 alpha/p91 to the nucleus. This nuclear translocation was followed by GFAP promoter activation and an up-regulation of GFAP mRNA and protein. Level of CNTF-alpha receptor mRNA, however, were unaffected by addition of the ligand. Transfection studies using an upstream 5'-flanking, 1.9-kb rat GFAP promoter linked to a luciferase reporter gene revealed CNTF-induced transcriptional activation within 1 h of ligand exposure. Moreover, serial-deleted constructs identified a distal (-1,857 to -1,546 bp) and a proximal (-384 to -106 bp) region as being important for CNTF-induced GFAP promoter activation. These two regions showed a strong degree of overlap for CNTF- and serum-induced activation of the GFAP gene. Analysis of the two regions revealed several cis-elements that are thought to be involved in GFAP regulation and/or the regulation of other genes by members of the interleukin-6 family of cytokines. Moreover, we are the first to report the presence of several putative CNTF-responsive elements within our identified distal and proximal regions in the GFAP gene promoter.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute-Phase Proteins / physiology
  • Animals
  • Blood Proteins / pharmacology
  • Blotting, Northern
  • Cell Line / chemistry
  • Cell Line / physiology
  • Ciliary Neurotrophic Factor
  • DNA-Binding Proteins / physiology
  • Gene Deletion
  • Gene Expression Regulation / drug effects
  • Genes, Reporter
  • Glial Fibrillary Acidic Protein / genetics*
  • Janus Kinase 1
  • Luciferases
  • Mutagenesis / physiology
  • Nerve Growth Factors / pharmacology
  • Nerve Tissue Proteins / pharmacology*
  • Oligodendroglia / chemistry
  • Oligodendroglia / cytology
  • Oligodendroglia / physiology*
  • Promoter Regions, Genetic / physiology
  • Protein-Tyrosine Kinases / physiology
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Rats
  • STAT3 Transcription Factor
  • Signal Transduction / drug effects*
  • Stem Cells / chemistry
  • Stem Cells / cytology
  • Stem Cells / physiology
  • Trans-Activators / physiology
  • Transcription, Genetic / physiology
  • Transfection


  • Acute-Phase Proteins
  • Blood Proteins
  • Ciliary Neurotrophic Factor
  • DNA-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • RNA, Messenger
  • STAT3 Transcription Factor
  • Stat3 protein, rat
  • Trans-Activators
  • Luciferases
  • Protein-Tyrosine Kinases
  • Jak1 protein, rat
  • Janus Kinase 1