Differential regulation of FGF-2 and FGFR-1 in rat cortical astrocytes by dexamethasone and isoproterenol.
We have used rat cortical astrocytes in culture to investigate the signaling pathways involved in the regulation of fibroblast growth factor-2 (FGF-2) and one of its high affinity receptor FGF receptor-1 (FGFR-1). These cells represent a source of different neurotrophic factors and play important roles in physiological and pathological conditions of the central nervous system. FGF-2 mRNA levels are increased by stimulation of beta-adrenergic receptors or exposure to glucocorticoid hormones and these effects are additive to each other. The regulation of FGFR-1, highly expressed in cultured astroglial cells, appears to be different. Isoproterenol produced an elevation of FGFR-1 mRNA levels, whereas dexamethasone decreased its expression alone or in the presence of isoproterenol, suggesting that the glucocorticoid pathway may predominate over the cAMP-induced up-regulation of the receptor. FGF-2 over-expression may produce different cellular responses depending on the concomitant regulation of its receptor and the cell phenotype where these changes do occur. These mechanisms can contribute to adaptive changes taking place in the CNS in different physiological and pathological situations.
Riva
M A
MA
Center for Neuropharmacology, Institute of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. mariva@imiucca.csi.unimi.it
Molteni
R
R
Racagni
G
G
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal; D001253:Astrocytes / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D018696:Neuroprotective Agents; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D003907:Dexamethasone; D003513:Cycloheximide; C496350:Fgfr1 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D007545:Isoproterenol; D009638:Norepinephrine