Effects of TGF-betas and bFGF on Astroglial Cell Growth and Gene Expression in Vitro

Transforming growth factor-betas (TGF-betas) 2 and 3 are expressed in murine embryonic astrocytes in vivo, but their cellular functions are not known. Primary cultures of rat neonatal astroglial cells express mRNA transcripts for TGF-betas 1, 2, and 3, as well as basic fibroblast growth factor (bFGF) and secrete TGF-beta1 and TGF-beta2 protein. TGF-beta3 protein levels cannot be determined at present. While bFGF is mitogenic for these cells, addition of TGF-betas 1, 2, or 3 alone has little effect. However, the effects of bFGF are modulated by TGF-betas in an isoform-specific fashion. Thus, TGF-beta3 and to a lesser extent TGF-beta2, but not TGF-beta1, can reduce the mitogenic effect of bFGF, but TGF-beta1 selectively leads to a change in cell morphology accompanied by colony formation. Basic FGF and TGF-betas alone, but not combinations of bFGF and TGF-betas, increase plasminogen activator (PA) activity of proliferating cultures, while on confluent cultures TGF-betas and bFGF show additive increases in PA activity. While bFGF and TGF-betas alone have little effect on expression of fibronectin, collagen I, or laminin B1 mRNA by these cells, the combination of TGF-betas and bFGF increases expression of collagen I mRNA. The expression of TGF-beta3, but not TGF-beta1 or TGF-beta2, mRNA is increased almost 10-fold by treatment with any TGF-beta isoform. These data show that TGF-betas alone have little effect on astrocyte growth and gene expression, but can alter effects of bFGF in an isoform-dependent manner. Changes in astrocyte proliferation and morphology, as well as expression of collagen and PA, induced by bFGF and TGF-beta1 are discussed in relation to astroglial scarring.