IMPAIRED REGULATION OF COLLAGEN PRO-ALPHA-1(I) MESSENGER-RNA AND CHANGE IN PATTERN OF COLLAGEN-BINDING INTEGRINS ON SCLERODERMA FIBROBLASTS

We explored the hypothesis that dermal fibroblasts isolated from patients suffering from systemic sclerosis are disturbed in their ability to interact functionally with native collagen fibers. Additionally, we investigated the expression of one collagen-binding integrin matrix receptor, alpha1beta1 on those cells. Two populations of primary dermal fibroblasts were established, one from patients with systemic sclerosis and one from normal subjects. When cultured for 24 h in free-floating collagen gels, both types of fibroblasts down-regulated the cellular content of collagen pro-alpha1(I) messenger ribonucleic acid, the systemic sclerosis fibroblasts less markedly than the normals. In normal, but not in systemic sclerosis fibroblasts, the kinetics of collagen gel contraction were directly proportional to the extent of the down-regulation. Fetal bovine serum stimulated collagen gel contraction in both populations. When grown in collagen gels in the presence of fetal bovine serum, no difference between systemic sclerosis and normal fibroblasts in capacity to down-regulate pro-alpha1(I) was observed. Collagen-binding beta1 integrins mediate the functional interactions between fibroblasts and the collagen fibers. To assess the cell surface expression of collagen-binding beta1 integrins on fibroblasts, we labeled cells with I-125 and subjected Triton X-100 extracts from them to immunoprecipitation with anti-beta1 integrin immunoglobulin G. Among the systemic sclerosis fibroblasts, a larger number of isolates expressed low amount of alpha1beta1 than did the fibroblasts isolated from normal individuals. Our data are compatible with the hypothesis that systemic sclerosis fibroblasts have a disturbed interaction with collagen fibers; this disturbance may in part be the result of an aberrant expression of collagen-binding beta1 integrins.