Extracellular matrix-dependent activation of syndecan-1 expression in keratinocyte growth factor-treated keratinocytes

Syndecan-1 is a major heparan sulfate proteoglycan of the epidermis. Its ex pression is strongly induced in migrating and proliferating keratinocytes d uring wound healing and, on the other hand, diminished or lost in invasive squamous cell carcinoma. We have recently found in the syndecan-1 gene an e nhancer (fibroblast growth factor-inducible response element (FIRE)) that a ctivates gene expression in wound edge keratinocytes (Jaakkola, P., Kontusa ari, S., Kauppi, T., Maatta, A., and Jalkanen, M. (1998) FASEB J. 12, 959-9 69). Now, we demonstrate that the activation of this enhancer by keratinocy te growth factor (KGF) is modulated by the components of the extracellular matrix (ECM), MCA-3D mouse immortal keratinocytes growing on fibrillar coll agen failed to activate FiRE and subsequently to induce syndecan-1 in respo nse to KGF, The same cells growing on fibronectin or laminin, however, incr eased FiRE-dependent reporter gene expression upon KGF treatment. The inhib ition of the KGF induction by collagen appears to be specific for signaling to FiRE, as the increase in cell proliferation by KGF was not affected. Th e effect was selective to KGF, as EGF-induction was independent on ECM comp osition. Changes in the transcription factor binding were not involved in t he differential activation of FiRE, as the levels and composition of the AP -1 complexes were unchanged. However, application of anisomycin, an activat or of Jun amino-terminal kinase, resulted in a lower response in cells grow ing on collagen compared with fibronectin, These results indicate that the composition of ECM and availability of growth factors can play a role in th e epidermal regulation of syndecan-1 expression and that FiRE is a novel ta rget for gene regulation by the extracellular matrix.