Transforming Growth Factor Beta in the Central Nervous System

By definition, growth factors are polypeptides that modulate the proliferation of mammalian cells by acting on their receptors at low concentration. Based on similarities in their sequences and their receptors, growth factors can be divided into several superfamilies including platelet-derived growth factors, epidermal growth factors, insulin-like growth factors, the transforming growth factor-beta (TGF-β) family, fibroblast growth factors, nerve growth factors (neurotrophins), erythropoietin, and hemopoietic colony stimulating factors. Transforming growth factors were originally named by their capacity to induce oncogenic transformation in rat kidney fibroblasts (Roberts et al., 1981). Transforming growth factor alpha has a structure and action similar to epidermal growth factor (Wells, 1999) and is not a subject of the present chapter. The TGF-β superfamily includes products of over 25 distinct genes. Comparison of the deduced amino acid sequences led to the definition of several groups within the superfamily, such as TGF-βs, bone morphogenetic proteins, multiple isoforms of activins and inhibins, anti-Mullerian hormone, decapentaplegic protein in Drosophila, and Vg1 protein in Xenopus (Burt & Law, 1994). There are five TGF-β sequences including three mammalian isoforms (TGF-β1, β2 and β3), which are encoded by unique genes located on different chromosomes (Lawrence, 1996). Besides the regulation of cell growth and division, TGF-βs can control the proliferation, survival, differentiation, migration, or function of cells depending on the circumstance. The best established activities of TGF-βs are the following: they inhibit proliferation of most cells, but can stimulate the growth of some mesenchymal cells; they enhance the formation of extracellular matrix; and they exert immunosuppressive effects (Roberts, 1998). Based on their effects on cells of the immune system, TGF-βs can also be considered cytokines (Kiefer et al., 1995).