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Regulation of astrocyte GFAP expression by TGF‐β1 and FGF‐2
Author(s) -
Reilly John F.,
Maher Pamela A.,
Kumari Vijaya G.
Publication year - 1998
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(199802)22:2<202::aid-glia11>3.0.co;2-1
Subject(s) - astrocyte , glial fibrillary acidic protein , biology , fibroblast growth factor , microbiology and biotechnology , fibroblast growth factor receptor , transforming growth factor , autophosphorylation , endocrinology , medicine , protein kinase a , receptor , immunology , kinase , biochemistry , central nervous system , immunohistochemistry
Astrocytes play a critical role in the development of the CNS and its response to injury and disease. A key indicator of astrocyte activation is the increased accumulation of intermediate filaments composed of glial fibrillary acidic protein (GFAP). Treatment of astrocytes in vitro with transforming growth factor‐β1 (TGF‐β1) produced little morphological change, but resulted in a significant increase in GFAP mRNA and protein. Treatment with basic fibroblast growth factor (FGF‐2) produced a dramatic change from a polygonal to a stellate morphology, and resulted in a significant decrease in GFAP mRNA and protein. FGF‐2 also inhibited the TGF‐β1‐mediated increase in GFAP mRNA and protein. Cycloheximide did not block the effects of TGF‐β1 or FGF‐2 on GFAP mRNA levels, but blocked the inhibitory effects of FGF‐2 on the TGF‐β1‐mediated increase in GFAP expression. All effects of FGF‐2 were blocked by co‐incubation with 5′‐methylthioadenosine, a specific inhibitor of FGF‐2‐induced tyrosine kinase activity and FGF receptor (FGFR) autophosphorylation. We also examined astrocyte expression of FGFR, and demonstrate the presence of FGFR 1 and 2, and lower levels of FGFR 3. Our results demonstrate that TGF‐β1 and FGF‐2 cause differential effects on the astrocyte cytoskeleton and morphology, suggesting an uncoupling of process outgrowth from GFAP synthesis. GLIA 22:202–210, 1998. © 1998 Wiley‐Liss, Inc.