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Mechanical Stress Regulates Syndecan‐4 Expression and Redistribution in Vascular Smooth Muscle Cells

&NA; Syndecan‐4 is a unique membrane‐associated heparan sulfate proteoglycan that colocalizes with integrin heterodimers in focal adhesion complexes. Because focal adhesions serve as a putative mechanotransduction system, we postulated that physical forces that are sensed by focal adhesions may regulate the expression and intracellular distribution of syndecan‐4 and thereby modulate cell movement and orientation. In this report, syndecan‐4 was identified as a transcriptionally regulated, immediate‐early gene in response to the application of oscillatory stress. This fluctuation was associated with coordinate changes in the concentration and compartmentalization of syndecan‐4 proteins. Specifically, syndecan‐4 was lost from the dorsal aspect of the cell membrane and translocated from its intracellular pool to the ventral cell surface. Dissociation of syndecan‐4 and vinculin from focal adhesions may contribute to promoting cell motility, because overexpression of syndecan‐4, in part, blocked this dissociation and also retarded mechanical stretch‐induced cell migration. These studies suggest that mechanical stress induces cell locomotion, in part, by the dynamic regulation of syndecan‐4 expression and relocation.