Fibroblast invasive migration into fibronectin/fibrin gels requires a previously uncharacterized dermatan sulfate-CD44 proteoglycan.
After tissue injury, fibroblast migration from the peri-wound collagenous stroma into the fibrin-laden wound is critical for granulation tissue formation and subsequent healing. Recently we found that fibroblast transmigration from a collagen matrix into a fibrin matrix required the presence of fibronectin. Several integrins-alpha 4 beta 1, alpha 5 beta 1, and alpha v beta 3-with known fibronectin binding affinity were necessary for this invasive migration. Here we examined another family of cell surface receptors: the proteoglycans. We found that dermatan sulfate was required for fibroblast migration into a fibronectin/fibrin gel. This conclusion was based on beta-xyloside inhibition of glycanation and specific glycosaminoglycan degradation. CD44, a cell surface receptor known to bind hyaluronan, not infrequently exists as a proteoglycan, decorated with various glycosaminoglycan chains including heparan sulfate and chondroitin sulfate, and as such can bind fibronectin. We found that CD44H, the non-spliced isoform of CD44, was necessary for fibroblast invasion into fibronectin/fibrin gels. Resting fibroblasts expressed mostly nonglycanated CD44H core protein, which became glycanated with chondroitin sulfate and dermatan sulfate, but not heparan sulfate, after a 24 h incubation with platelet-derived growth factor, the stimulus used in the migration assay. These results demonstrate that dermatan sulfate-CD44H proteoglycan is essential for fibroblast migration into fibrin clots and that platelet-derived growth factor, the stimulus for migration, induces the production of chondroitin-sulfate- and dermatan-sulfate-glycanated CD44H.
Clark
Richard A F
RA
Department of Dermatology, School of Medicine, SUNY at Stony Brook, New York, 11794-8165, USA. richard.clark@sunysb.edu
Lin
Fubao
F
Greiling
Doris
D
An
Jianqang
J
Couchman
John R
JR
D000328:Adult; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D003871:Dermatan Sulfate / Q000378:metabolism*; D020405:Dermis / Q000166:cytology*; D005109:Extracellular Matrix / Q000378:metabolism; D005337:Fibrin / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology; D005782:Gels; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D014945:Wound Healing / Q000502:physiology
D011508:Chondroitin Sulfate Proteoglycans; D005353:Fibronectins; D005782:Gels; D018960:Hyaluronan Receptors; D010982:Platelet-Derived Growth Factor; C032649:dermatan sulfate proteoglycan; D003871:Dermatan Sulfate; D005337:Fibrin