Myofibroblasts from scleroderma skin synthesize elevated levels of collagen and tissue inhibitor of metalloproteinase (TIMP-1) with two forms of TIMP-1.

Cultured fibroblasts derived from skin biopsies from scleroderma patients and normal individuals were examined for the presence of smooth muscle alpha-actin, a marker for myofibroblasts. Six of eight scleroderma cell lines were found to be 50% or more positive for alpha-actin while three of four normal lines and one cell line derived from unaffected skin of a scleroderma patient were less than 10% positive. The cultured fibroblasts from affected scleroderma skin were largely myofibroblasts, a phenotype found in biopsies of scleroderma tissue, as well as other fibrotic lesions, wound healing, and tumor desmoplasia. The data support the hypothesis that a certain activated fibroblast phenotype predominates in scleroderma. The activated fibroblast is the myofibroblast. Both collagen and TIMP (tissue inhibitor of metalloproteinases) were elevated in the alpha-actin positive (myofibroblast enriched) cultures. In addition, the myofibroblast-enriched cultures displayed a more prominent TIMP doublet band pattern on SDS-polyacrylamide gel electrophoresis.