Elsevier

Neuroscience Research

Volume 114, January 2017, Pages 16-29
Neuroscience Research

Analysis of the expression of the Wnt family of proteins and its modulatory role on cytokine expression in non activated and activated astroglial cells

https://doi.org/10.1016/j.neures.2016.08.003Get rights and content
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Highlights

  • We analyzed the expression and inflammatory functions of Wnts in astrocytes.

  • Non-activated astrocytes express numerous Wnt ligands, receptors and regulators.

  • Astroglial expression of many Wnt-related molecules suffered post-activation changes.

  • Wnt1 and 5a modulated astroglial IL-1β but not TNFα, IL-6, TGFβ1 and GFAP expression.

  • Wnts may be involved in how astrocytes interact with the normal and damaged CNS.

Abstract

Despite the essential functions of astrocytes and the emerging relevance of the Wnt family of proteins in the CNS under physiological and pathological conditions, the astroglial expression of this family of proteins and its potential modulatory role on astroglial activation is almost unknown. Thus, we have evaluated the expression of all Wnt ligands, receptors and regulators, and the activation state of Wnt-related signaling pathways in non-activated and differentially activated astroglial cultures. We found that numerous Wnt ligands, receptors and regulators were expressed in non-activated astrocytes, while the Wnt-dependent pathways were constitutively active. Moreover, the expression of most detectable Wnt-related molecules and the activity of the Wnt-dependent pathways suffered post-activation variations which frequently depended on the activation system. Finally, the analysis of the effects exerted by Wnt1 and 5a on the astroglial expression of prototypical genes related to astroglial activation showed that both Wnt ligands increased the astroglial expression of interleukin 1β depending on the experimental context, while did not modulate tumor necrosis factor α, interleukin 6, transforming growth factor β1 and glial fibrillary acidic protein expression. These results strongly suggest that the Wnt family of proteins is involved in how astrocytes modulate and respond to the physiological and pathological CNS.

Abbreviations

CNS
central nervous system
BBB
blood brain barrier
Fz
Frizzled
ROR
receptor tyrosine kinase-like orphan receptor
PTK7
protein tyrosine kinase 7
PCP
planar cell polarity
Wif
Wnt inhibitory factor
Dkk
Dickkopf
sFRP
secreted Frizzled-related protein
Rspo
R-spondin
NA
non-activated
SC
lesioned spinal cord extract
cm
centimeter
GFAP
glial fibrillary acidic protein
LPS
lipopolysaccharide
hpa
hours post-activation
RT
room temperature
BSA
bovine serum albumin
qRT-PCR
quantitative Real-Time PCR
TGF
transforming growth factor
TNF
tumor necrosis factor
IL
interleukin
GAPDH
glyceraldehyde-3-phosphate dehydrogenase
Ct
cycle threshold
p-CaMKII
phospho Ca2+/calmodulin-dependent protein kinase II
p-SAPK/JNK
phospho stress-activated protein kinase/c-Jun N-terminal kinase
dpa
days post-activation

Keywords

Astrocyte
Wnt ligand
Wnt receptor
Wnt regulator
Wnt signaling
In vitro
Cytokine expression

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