Transcriptional Regulation of Syndecan-1 Expression by Growth Factors

Abstract

Syndecan-1 is a prototype member of a family of transmembrane heparan sulfate proteoglycans. Syndecan-1 binds extracellular matrix components and fibroblast growth factors (FGFs) and modifies the function of FGFs. Syndecan-1 is constitutively expressed by several epithelial cells, but expression is also induced during many biological phenomena, such as tissue regeneration and the epithelial-mesenchymal interactions during organ development. Growth factors have been the prime candidates to induce syndecan-1 expression in these situations. In fibroblasts syndecan-1 is induced by FGF-2 and in keratinocytes by epidermal growth factor (EGF) and keratinocyte growth factor (KGF). The search for cis-acting elements regulating the growth factor-induced syndecan-1 expression has led to identification of a novel FGF-inducible response element (FiRE). FiRE is activated in fibroblasts and keratinocytes by the same growth factors that induce syndecan-1 expression in these cells. In adult tissues the activation of FiRE is restricted to migrating keratinocytes of healing wounds. The composition of the transcription factor binding to FiRE differs depending on the cell type and the activating growth factor. The FiRE provides a powerful tool for studies on growth factor specificity and regeneration of tissues. Moreover, it implies a novel transcriptional link that creates an FGF action-controlling autoregulatory loop between the heparan sulfate proteoglycans and the heparin-binding FGFs.