Hyaluronic acid metabolism in keloid fibroblasts.
Hyaluronic acid (HA), an important component of the tissue extracellular matrix, is a ubiquitous glycosaminoglycan (GAG) that forms a pericellular coat on the surface of cells. It has been speculated that this pericellular HA boundary may localize cytokines, such as transforming growth factor-beta 1, which is known to stimulate collagen production. The purpose of this study was to examine the role of HA and its cell surface receptor (CD44), an active participant in HA degradation, as they relate to keloid formation. Dermal excisions from both normal patients (n = 13) and keloid patients (n = 13) were analyzed for HA content using an alcian blue staining technique. Fibroblast cell cultures were used to quantitate HA synthesis and CD44 receptor density. Histological analyses showed a greater HA content in keloid tissue compared with normal dermal tissue. In agreement with this observation, keloid fibroblasts were found to synthesize significantly more HA than normal dermal fibroblasts (2469 +/- 483 cpm versus 1122 +/- 256 cpm, P = .02). Treatment of keloid fibroblasts with triamcinolone acetonide reduced the level of HA synthesis to that of normal fibroblasts (1560 +/- 477 cpm versus 1293 +/- 264 cpm, P = .6). However, there was no significant difference in HA receptor density on keloid cells compared with normal skin fibroblasts. Therefore, the increased HA deposits found in keloids are attributable to increased synthesis rather than to decreased degradation mediated by the CD44 receptor.
D000293:Adolescent; D000328:Adult; D000423:Alcian Blue; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D004396:Coloring Agents; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis / Q000235:genetics / Q000502:physiology; D006820:Hyaluronic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D007627:Keloid / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014222:Triamcinolone Acetonide / Q000494:pharmacology
D004396:Coloring Agents; D018960:Hyaluronan Receptors; D016212:Transforming Growth Factor beta; D006820:Hyaluronic Acid; D003094:Collagen; D014222:Triamcinolone Acetonide; D000423:Alcian Blue