Regulation of astrocytic tenascin by basic fibroblast growth factor.
Extracellular matrix (ECM) molecules have been implicated in the regulation of neuronal adhesion and neurite outgrowth both during development and after injury. It has been demonstrated in our laboratory that astrocytes are heterogeneous in expression of the ECM molecule tenascin. High-tenascin astrocytes have a reduced ability to support neurite outgrowth. In addition, astrocytes treated with exogenous basic fibroblast growth factor (bFGF) supported reduced neuronal growth and adhesion. In the current study, the hypothesis was tested that bFGF could increase the expression of tenascin by these cells. Basic FGF was added to cultures of rat cerebral cortical astrocytes at concentrations of up to 30 ng/ml, concentrations shown to have a significant effect on neuronal adhesion. Tenascin levels were evaluated by Western blot analysis of both cell extracts and conditioned media and also by immunocytochemistry techniques. Tenascin levels began to increase after 24-48 hr and continued to increase throughout 8 days in culture. The increase in tenascin was concentration-dependent, with the largest increase seen at 5 ng/ml bFGF. Tenascin production was increased approximately 5.5-fold in serum-containing medium but only about 2-fold in serum-free medium. When heparin (10 micrograms/ml) was included along with bFGF in serum-free medium, tenascin production was further enhanced. The bFGF treatment was discontinued after 8 days, and the cells were maintained for an additional 8 days in culture. Tenascin levels returned to control values, demonstrating that the bFGF effect is transient. It is our hypothesis that the action of bFGF during injury may evoke the induction of tenascin on astrocytes, thereby reducing regeneration in the central nervous system.
Meiners
S
S
Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Piscataway 08854.
Marone
M
M
Rittenhouse
J L
JL
Geller
H M
HM
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001769:Blood; D002417:Cattle; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis*; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D005353:Fibronectins / Q000096:biosynthesis; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012967:Sodium Dodecyl Sulfate; D019063:Tenascin
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D019063:Tenascin; D016222:Fibroblast Growth Factor 2; D012967:Sodium Dodecyl Sulfate; D006493:Heparin