Expression of different glycosaminoglycan synthetic phenotypes by lapine dermal and dermal wound fibroblasts

Synthesis of extracellular matrix by dermal fibroblasts is an important component of cutaneous wound repair. Scar remodeling and maturation is generally seen as the result of a fibroblast-regulated equilibrium between production and degradation of specific matrix constituents. Fibroblasts from normal dermis, reparative granulation tissue and mature scars were compared in vitro in terms of their ability to produce extracellular glycosaminoglycans (GAGs). All cell lines secreted dermatan sulfate (DS) and chondroitin sulfate (CS) into the culture medium. Hyaluronate (HA) was detected in medium from mature granulation tissue and scar cells, but little or none was found in medium from early granulation tissue or skin cells. In medium from normal skin fibroblasts, an unusual GAG was identified as a potential variant of DS on the basis of co-migration with HA but susceptibility to digestion with chondroitinase ABC. Heparan sulfate (HS) was the major pericellular GAG of all cultures except the mature scar cells, which contained a predominance of DS. A second pericellular GAG was identified as CS in mature granulation tissue cells, scar cells and skin cells; while HA was identified in the pericellular matrix of early granulation tissue cells. In addition, fibroblasts from both skin and early granulation tissue contained a GAG believed to be a variant of CS. These differences in GAG synthesis/secretion between cells maintained under identical culturing conditions could indicate either that distinct fibroblastic substrains exist during different stages of healing or that influences present during the healing process induce stable phenotypic alterations that are maintained through explant culturing and subsequent subcultivation.