Transforming growth factor-betas inhibit mitogen-stimulated proliferation of astrocytes

We have studied the influence of three members of the transforming growth factor-beta (TGF-beta) family of multifunctional growth factors on the proliferation of cultured astrocytes isolated from newborn mouse cerebral cortex. Although TGF-beta s 1, 2, and 3 cause only a small reduction in the low level of astrocyte proliferation occurring in chemically defined medium, they each inhibit the effects of five astrocyte mitogens (bFGF, EGF, PDGF, IL-1 alpha, and IL-2). Inhibition is observed when astrocytes are exposed to mitogen and TGF-beta at the same time and when they are exposed to TGF-beta prior to, and separately from, mitogen. This latter effect appears to be due to the binding of TGF-beta s to astrocyte-secreted extracellular matrix. These findings raise the possibility that TGF-beta may co-operate with other growth factors to control astrocyte proliferation in vivo.