Increased glycosaminoglycan accumulation as a genetic characteristic in cell cultures of one variety of dominant dystrophic epidermolysis bullosa.
Fibroblast cultures from patients with dominant dystrophic epidermolysis bullosa of the albopapuloid variety display deranged glycosaminoglycan metabolism. These cells accumulate increased amounts of sulfated glycosaminoglycans. The mechanism for the greater content of glycosaminoglycans appears to be related to increased synthesis. During the first 6-12 h, intracellular labeled glycosaminoglycans accumulated in the dominant dystrophic epidermolysis bullosa cells at about twice the rate as that of control fibroblasts. In addition, secretion of sulfated glycosaminoglycans was two- to threefold greater than in control cultures. In contrast, both pulse-chase and cross-correction experiments failed to show any evidence for defective degradation of the material. The biochemical trait is genetically specific for albopapuloid dominant dystrophic epidermolysis bullosa, since fibroblasts from patients with other varieties of epidermolysis bullosa did not accumulate increased glycosaminoglycans. The data suggest that in vitro abnormality in glycosaminoglycan metabolism could serve as an important marker for this variety of epidermolysis bullosa and be of genetic and prognostic value in the sporadic patient with epidermolysis bullosa. Although the precise relationship of the defect to the disease has not yet been defined, it is possible that excessive tissue accumulation of glycosaminoglycans may alter collagen fibril deposition, thus, impairing the structural integrity of the skin and leading to posttraumatic blisters and erosions that characterize the disease.
D002478:Cells, Cultured; D004705:Endocytosis; D004820:Epidermolysis Bullosa / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D012867:Skin / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism
D006025:Glycosaminoglycans; D013431:Sulfates