SYNDECAN-1 EXPRESSION IS DOWN-REGULATED DURING MYOBLAST TERMINAL DIFFERENTIATION - MODULATION BY GROWTH-FACTORS AND RETINOIC ACID

Syndecan-1 is an integral membrane proteoglycan involved in the intera ction of cells with extracellular matrix proteins and growth factors. It is transiently expressed in several condensing mesenchymal tissues after epithelial induction. In this study we evaluated the expression of syndecan-1 during skeletal muscle differentiation. The expression o f syndecan-1 as determined by Northern blot analyses and immunofluores cence microscopy is down-regulated during differentiation. The transcr iptional activity of a syndecan-1 promoter construct is also down-regu lated in differentiating muscle cells. The decrease in syndecan-1 gene expression is not dependent on the presence of E-boxes, binding sites for the MyoD family of transcription factors in the promoter region, or myogenin expression. Deletion of the region containing the E-boxes or treatment of differentiating cells with sodium butyrate, an inhibit or of myogenin expression, had no effect on syndecan-1 expression. Bas ic fibroblast growth factor and transforming growth factor type beta, which are inhibitors of myogenesis, had little effect on syndecan-1 ex pression. When added together, however, they induced syndecan-1 expres sion. Retinoic acid, an inducer of myogenesis, inhibited syndecan-1 ex pression and abolished the effect of the growth factors. These results indicate that syndecan-1 expression is down-regulated during myogenes is and that growth factors and retinoic acid modulate syndecan-1 expre ssion by a mechanism that is independent of myogenin.