Biology of the scleroderma fibroblast

Abnormalities of matrix biosynthesis by systemic sclerosis fibroblasts underlie the cutaneous and visceral fibrosis seen in this disease. The fundamental basis of the abnormal fibroblast phenotype has not been determined but primary metabolic abnormalities, responses to abnormal environmental signals, and clonal selection have all been hypothesized to play a role. In the past year, evidence supporting each of these explanations was forthcoming. In a study of Choctaw Indians with a high incidence of scleroderma, it was shown that genetic linkage to fibrillin may play a role. This should be considered in light of demonstrated abnormalities of fibrillin structure in the tight skin mouse. Other studies have shown that abnormalities of transforming growth factor beta receptor levels, abnormalities of production and response to tissue inhibitor of matrix metal-loproteinase, and abnormalities of response to endothelial cell factors are all present in scleroderma fibroblasts. In addition to these studies in scleroderma fibroblasts, work elucidating the role of transcription factors Sp1, Sp3, and cKrox in regulating collagen metabolism provided important data upon which future studies may build.