Transforming and Heparin-Binding Growth Factors: Cellular Receptors and Biological Responses in Icratinocytes and Melanocytes

Abstract

The transforming growth factors and heparin-binding/fibroblast growth factors are major classes of polypeptide growth factors that regulate cell growth and differentiation. Transforming growth factor type α (TGF-α) is a potent mitogen for human keratinocytes. The cellular receptor for TGF-α is the epidermal growth factor (EGF) receptor. TGF-α is produced and secreted by cultured keratinocytes. Autoinduction of TGF-a expression by keratinocytes is one mechanism of regulation that may modulate autocrine/paracrine control of epidermal growth. Cultures of normal human melanocytes do not express EGF receptor, and TGF-a or EGF is not mitogenic for epidermal-derived pigment cells. Transforming growth factor type β (TGF-β) reversibly arrests growth of normal keratinocytes and melanocytes in vitro. Keratinocytes secrete a latent form of TGF-β. Following protein activation and binding to specific cellular receptors, TGF-β exerts multiple biological effects on epithelial and mesenchymal cells of skin.

Fibroblast growth factors (FGFs) stimulate proliferation of normal epidermal keratiriocytes and melanocytes in culture. Distinct cell membrane receptors for the FGFs mediate mitogenesis and other differentiation-related programs in responsive cell types. Basic FGF gene expression is induced or markedly enhanced by serum treatment of normal dermal fibroblasts and by exposure of human keratinocytes to activated TGF-β. TGFs and FGFs are constitutively expressed or are induced to be expressed by epidermal and fibroblast skin cells in culture. Keratinocytes, melanocytes, and other skin cells also express functional receptors for the TGFs and FGFs. These findings support the basic concept of locally mediated regulation of epidermal growth and differentiation via autocrine/paracrine cellular communication. The TGFs, FGFs, their receptors, and, undoubtedly, other growth factors/receptors function within the larger network of cellular signals to maintain epidermal and cutaneous homeostasis.