TY - JOUR

T1 - Fibroblast invasive migration into fibronectin/fibrin gels requires a previously uncharacterized dermatan sulfate-CD44 proteoglycan.

AU - Clark, Richard A F

AU - Lin, Fubao

AU - Greiling, Doris

AU - An, Jianqang

AU - Couchman, John R

N1 - Keywords: Adult; Antigens, CD44; Cell Movement; Cells, Cultured; Dermatan Sulfate; Dermis; Extracellular Matrix; Fibrin; Fibroblasts; Fibronectins; Gels; Humans; Platelet-Derived Growth Factor; Proteochondroitin Sulfates; Wound Healing

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

U2 - 10.1046/j.0022-202X.2004.22205.x

DO - 10.1046/j.0022-202X.2004.22205.x

M3 - Journal article

C2 - 15009704

VL - 122

SP - 266

EP - 277

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 2

ER -