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, Levels 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.

Ciliary neurotrophic factor activates JAK/Stat signal transduction cascade and induces transcriptional expression of glial fibrillary acidic protein in glia lcells / Kahn, Ma; Huang, Cj; Caruso, Alessandra Sebastiana Maria; Barresi, V; Nazarian, R; Condorelli, Df; DE VELLIS, J.. - In: JOURNAL OF NEUROCHEMISTRY. - ISSN 0022-3042. - 68:(1997), pp. 1413-1423. [10.1046/j.1471-4159.1997.68041413.x]

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

CARUSO, Alessandra Sebastiana Maria;
1997

Abstract

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, Levels 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.
1997
01 Pubblicazione su rivista::01a Articolo in rivista
Ciliary neurotrophic factor activates JAK/Stat signal transduction cascade and induces transcriptional expression of glial fibrillary acidic protein in glia lcells / Kahn, Ma; Huang, Cj; Caruso, Alessandra Sebastiana Maria; Barresi, V; Nazarian, R; Condorelli, Df; DE VELLIS, J.. - In: JOURNAL OF NEUROCHEMISTRY. - ISSN 0022-3042. - 68:(1997), pp. 1413-1423. [10.1046/j.1471-4159.1997.68041413.x]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/143234
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