Regulation of astrogliosis by fibroblast growth factor-2 and transforming growth factor-beta 1

Astrocytes comprise the most numerous cellular element of the brain and participate in many aspects of normal nervous system development and function. In addition, astrocytes exhibit one of the earliest and most remarkable cellular responses following a variety of insults to the central nervous system. Basic fibroblast growth factor (FGF-2) has mitogenic and morphogenic effects on astrocytes, and an interaction between FGF-2 and its receptor is likely to play a role in astrogliosis. Expression of FGF receptor (FGFR) was increased on astrocytes adjacent to a brain wound by day two post-lesion, increased further through day ten and decreased to control values by day 28. These data demonstrate a time course for astrocyte expression of FGFR that precedes and parallels the time course for astrocyte hypertrophy, and suggest that endogenous FGF-2, acting directly on FGFR-expressing astrocytes, may contribute to astrogliosis.; Previous studies have shown that injection of FGF-2 into a brain wound enhances astrocyte hypertrophy in areas adjacent to the lesion. Co-administration of the low-affinity FGF receptor heparan sulfate (HS) with FGF-2 enhanced astrocyte hypertrophy at a greater distance from the lesion than FGF-2 alone. These results suggest that the FGF-2+HS complex may gain entry into the brain more readily, reach higher concentrations and be more effective as a neurotrophic agent.; A key indicator of astrocyte activation is the increased accumulation of glial fibrillary acidic protein (GFAP). Treatment of astrocytes in vitro with FGF-2 resulted in dramatic morphological change accompanied by a decrease in the expression of GFAP. Treatment with transforming growth factor-{dollar}beta{dollar}1 (TGF-{dollar}beta{dollar}1) produced little morphological change, but resulted in a significant increase in GFAP mRNA and protein. These results demonstrate that TGF-{dollar}beta{dollar}1 and FGF-2 cause differential effects on the astrocyte cytoskeleton and morphology, suggesting an uncoupling of process outgrowth from GFAP synthesis.; These studies have further elucidated the roles of FGF-2 and TGF-{dollar}beta{dollar}1 in the astrocyte response to injury, and helped to provide a better understanding of the regulation of the astrocyte hypertrophy which follows central nervous system trauma.