Regulation of astrocyte GFAP expression by TGF-beta1 and FGF-2.
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-beta1 (TGF-beta1) 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-beta1-mediated increase in GFAP mRNA and protein. Cycloheximide did not block the effects of TGF-beta1 or FGF-2 on GFAP mRNA levels, but blocked the inhibitory effects of FGF-2 on the TGF-beta1-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-beta1 and FGF-2 cause differential effects on the astrocyte cytoskeleton and morphology, suggesting an uncoupling of process outgrowth from GFAP synthesis.
Reilly
J F
JF
Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis 95616, USA.
Maher
P A
PA
Kumari
V G
VG
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D003513:Cycloheximide / Q000494:pharmacology; D003839:Deoxyadenosines / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D011233:Precipitin Tests; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D013872:Thionucleosides / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D003432:Cross-Linking Reagents; D003839:Deoxyadenosines; D005904:Glial Fibrillary Acidic Protein; D007457:Iodine Radioisotopes; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D013872:Thionucleosides; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; C008500:5'-methylthioadenosine; D003513:Cycloheximide