Three-dimensional migration of human adult dermal fibroblasts from collagen lattices into fibrin/fibronectin gels requires syndecan-4 proteoglycan.
Fibroblast migration from the peri-wound collagenous stroma into the fibrin-laden wound is critical for granulation tissue formation and subsequent healing. Previously we found that fibroblast transmigration from a collagen matrix into a fibrin matrix required fibronectin (FN). Integrins alpha4beta1, alpha5beta1, and alphavbeta3 and dermatan sulfate CD44 were required for this invasive migration. Here we demonstrated that syndecan-4, a transmembrane heparan sulfate (HS) proteoglycan, known to bind FN, is also required for fibroblast invasive migration of a fibrin/FN gel. This conclusion was based on fibroblast migration using two independent means of disrupting syndecan-4: heparinase degradation of HS glycosaminoglycans or suppression of syndecan-4 core protein with antisense oligodeoxynucleotides. Isolated syndecan-4 from these fibroblasts bound Hep II recombinant constructs FN III12-V15>FN III12-15>FN III12-14 but did not bind the IIICS (V) domain. Furthermore, platelet-derived growth factor (PDGF), which is required to stimulate fibroblast migration, markedly increased cell levels of syndecan-4 core protein in a time and concentration-dependent fashion. PDGF also induced upregulation of syndecan-4 at transcriptional level as determined by RT-PCR. These results demonstrate that syndecan-4 is essential for fibroblast invasive migration into fibrin clot and that PDGF, the stimulus for migration, induces increased syndecan-4 core protein expression.
Lin
Fubao
F
Department of Biomedical Engineering, School of Medicine and College of Engineering and Applied Science, SUNY at Stony Brook, Stony Brook, New York 11794-8165, USA.
Ren
Xiang-Dong
XD
Doris
Greiling
G
Clark
Richard A F
RA
D000328:Adult; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology*; D005353:Fibronectins / Q000378:metabolism*; D005782:Gels; D006497:Heparan Sulfate / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011509:Proteoglycans / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000166:cytology*; D053671:Syndecan-4
D003094:Collagen; D005337:Fibrin; D005353:Fibronectins; D005782:Gels; D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D010982:Platelet-Derived Growth Factor; D011509:Proteoglycans; D012333:RNA, Messenger; D053671:Syndecan-4; C508304:SDC4 protein, human