Regulation of DNA synthesis by fibronectin and its proteolysis products in skin fibroblasts of healthy donors and patients with systemic scleroderma and rheumatoid arthritis

Abstract

To study the effect of fibronectin isolated from plasma and culture media and the effect of its tryptic hydrolyzates on DNA synthesis, cultured skin fibroblasts of healthy donors and these of patients with systemic scleroderma (SSD) and rheumatoid arthritis (RA) were employed. It was shown that both fibronectin and total products of its proteolysis markedly stimulated DNA synthesis only in skin fibroblasts of patients with SSD. Fibronectin fragments inhibited DNA synthesis in all fibroblast strains studied. The effect of fibronectin and all its Gel fragments on the DNA synthesis in skin fibroblasts of patients with SSD was dose-dependent. The activity of total fibronectin tryptate, Gel-fragment-free tryptate, and Gel fragments themselves depended on the duration of fibronectin proteolysis, i. e. on the size of the fragments obtained. Culture media collected after treatment of fibroblast monolayer with trypsin and subsequent removal of fibronectin Gel fragments had mitogenic effect on skin fibroblasts, especially on those of patients with SSD and RA. It is supposed that fibronectin Gel fragments are inhibitors of growth factors produced by fibroblasts. The results suggest that fibronectin and its fragments have an important regulatory role in fibroblast proliferation.