Collagen synthesis and degradation by epidermolysis bullosa fibroblasts

Collagen synthesis was measured in fibroblasts cultured from the skin of six patients with epidermolysis bullosa simplex, from six patients with dystrophic epidermolysis bullosa and six age-matched controls without skin disease. Both groups of patients' fibroblasts synthesized approximately twice as much collagen (dpm/cell) as the controls. Synthesis of other proteins showed a smaller increase. Collagenase activity in culture media from four fibroblast lines per group was measured, using a 3H-collagen substrate, both before and after trypsin treatment to activate procollagenase. As expected, the dystrophic group had the highest activity (30% more than controls) and the result was little affected by trypsin: the enzyme appeared to be in active form. Enzyme activity in the simplex group was increased from 67% to 114% of control values by trypsin treatment. The excessive collagen synthesis in both dystrophic and simplex fibroblasts may be a consequence of their greater collagenase activity and suggests an unsuspected dermal involvement in epidermolysis bullosa simplex. Our data confirm an excessive secretion of collagenase by dystrophic fibroblasts but suggest that the enzyme's state of activation may be the important aetiological feature of the dystrophic disease.