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Ciliary Neurotrophic Factor Activates JAK/Stat Signal Transduction Cascade and Induces Transcriptional Expression of Glial Fibrillary Acidic Protein in Glial Cells
Author(s) -
Kahn M. A.,
Huang C. J.,
Caruso A.,
Barresi V.,
Nazarian R.,
Condorelli D. F.,
De Vellis J.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68041413.x
Subject(s) - ciliary neurotrophic factor , glial fibrillary acidic protein , biology , microbiology and biotechnology , signal transduction , astrogliosis , regulation of gene expression , neurotrophic factors , gene , receptor , endocrinology , immunology , genetics , central nervous system , immunohistochemistry
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 Stat1α/p91 to the nucleus. This nuclear translocation was followed by GFAP promoter activation and an up‐regulation of GFAP mRNA and protein. Levels of CNTF‐α 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.