1. Departments of Dermatology and Biomedical Engineering, School of Medicine, SUNY at Stony Brook, New York
2. ^*Department of Cell Biology and Cell Adhesion and Matrix Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA

Correspondence: Richard A. F. Clark, MD, Departments of Biomedical Engineering, Dermatology, and Medicine, SUNY at Stony Brook, Stony Brook, NY 11794-8165. Email: richard.clark@sunysb.edu

Received 23 December 2003; Revised 9 May 2003; Accepted 30 June 2003; Published online 12 February 2004.

Abstract

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-41, 51, and v3-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 -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.