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Regulation of astrocyte GFAP expression by TGF-beta1 and FGF-2
J F Reilly1, P A Maher, V G Kumari
1Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis 95616, USA.
Glia
|April 16, 1998
Summary
Transforming growth factor-beta1 (TGF-beta1) increases glial fibrillary acidic protein (GFAP) in astrocytes, while fibroblast growth factor-2 (FGF-2) decreases it. FGF-2 also inhibits TGF-beta1’s effects, impacting astrocyte morphology and GFAP synthesis.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Astrocytes are crucial for central nervous system (CNS) development and response to injury.
- Glial fibrillary acidic protein (GFAP) accumulation indicates astrocyte activation.
Purpose of the Study:
- To investigate the differential effects of TGF-beta1 and FGF-2 on astrocyte morphology and GFAP expression.
- To elucidate the signaling pathways involved in these cellular responses.
Main Methods:
- Primary astrocyte cultures were treated with TGF-beta1 and/or FGF-2.
- GFAP mRNA and protein levels were quantified.
- Inhibitors of protein synthesis (cycloheximide) and FGF receptor (FGFR) signaling (5'-methylthioadenosine) were used.
- FGFR expression in astrocytes was analyzed.
Main Results:
- TGF-beta1 increased GFAP mRNA and protein with minimal morphological change.
- FGF-2 induced a shift to stellate morphology and decreased GFAP mRNA and protein.
- FGF-2 inhibited TGF-beta1-induced GFAP increases, an effect blocked by cycloheximide.
- FGF-2 effects were mediated via FGFR tyrosine kinase activity.
- Astrocytes express FGFR 1, 2, and 3.
Conclusions:
- TGF-beta1 and FGF-2 exert distinct regulatory effects on astrocyte cytoskeleton and morphology.
- These growth factors appear to uncouple astrocyte process outgrowth from GFAP synthesis.
- FGFR signaling plays a key role in mediating FGF-2's effects on astrocytes.