PR-39 coordinates changes in vascular smooth muscle cell adhesive strengthand locomotion by modulating cell surface heparan sulfate-matrix interactions

PR-39 is proline-rich peptide produced at sites of tissue injury. While the functional properties of this peptide have not been fully defined, PR-39 m ay be an important regulator of processes related to cell-matrix adhesion s ince it reportedly upregulates syndecan-4, which is a critical determinant of focal adhesion formation. The ability of PR-39 to modulate the adhesion and chemokinetic migration behavior of arterial smooth muscle cells (SMCs) in a fashion coordinated with syndecan-4 expression was investigated. Treat ment of SMCs with PR-39 did not alter syndecan-1 mRNA, but did induce a two -fold increase in syndecan-4 mRNA (P <0.0001) and significantly enhanced ce ll surface expression of both syndecan-4 (P <0.01) and heparan sulfate (HS) (P <0.05). These observations were consistent with an observed increase in cell-matrix adhesive strength (P <0.05) and a reduction in cell speed (P < 0.01) on fibronectin-coated substrates. incubation of PR-39 treated cells w ith a soluble fibronectin derived heparin-binding peptide, as a competitive inhibitor of heparan sulfate/matrix interactions, abolished these effects. These data suggest that PR-39 mediated alterations of cell adhesion and mo tility may be related, in part, to the increased expression of heparan sulf ate glycosaminoglycans (GAGs) that accompany the upregulation of cell surfa ce syndecan-4. Futhermore, this investigation supports the notion that fact ors which control syndecan-4 expression may play an important role in regul ating adhesion related cell processes. (C) 2001 Wiley-Liss, Inc.