PR-39 coordinates changes in vascular smooth muscle cell adhesive strength and 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 may be an important regulator of processes related to cell-matrix adhesion since 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. Treatment 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 cell 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 with 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 motility may be related, in part, to the increased expression of heparan sulfate glycosaminoglycans (GAGs) that accompany the upregulation of cell surface syndecan-4. Furthermore, this investigation supports the notion that factors which control syndecan-4 expression may play an important role in regulating adhesion related cell processes.
Chon
J H
JH
School of Chemical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
Houston
M M
MM
Xu
C
C
Chaikof
E L
EL
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism* / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D053671:Syndecan-4; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D023181:Antimicrobial Cationic Peptides; D005353:Fibronectins; D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; D053671:Syndecan-4; C508307:Sdc4 protein, rat; C072212:PR 39