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.
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201.
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Kirk
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Chua
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Chua
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D000199:Actins / Q000032:analysis / Q000096:biosynthesis; D001706:Biopsy; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D008715:Methionine / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism; D011392:Proline / Q000378:metabolism; D012016:Reference Values; D012594:Scleroderma, Localized / Q000378:metabolism* / Q000473:pathology; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D013462:Sulfur Radioisotopes; D019714:Tissue Inhibitor of Metalloproteinases; D014316:Tritium
D000199:Actins; D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D013462:Sulfur Radioisotopes; D019714:Tissue Inhibitor of Metalloproteinases; D014316:Tritium; D003094:Collagen; D011392:Proline; D008715:Methionine