title: Mechanisms of skin fibrosis in systemic sclerosis.
abstract: Systemic sclerosis (SSc) or scleroderma is an acquired disorder which typically results in fibrosis of the skin and internal organs. Skin fibrosis, the hallmark of this disease, is defined as excess deposition and accumulation of extracellular matrix, mainly type I collagen, in the dermis. Dermal fibroblasts isolated from lesional skin of SSc patients and cultured in vitro exhibit increased synthesis of collagen and decreased collagenase activity, consistent with the disease phenotype. This review focuses on the recent progress in the research for molecular mechanisms of skin fibrosis in SSc. The upregulated collagen production at transcriptional level in SSc fibroblasts involves various regulators including cytokines or transcription factors. Among them, transforming growth factor (TGF)-beta/Smad signaling is likely to play a key role in the pathogenesis of SSc, and the autocrine TGF-beta signaling hypothesis can explain intrinsic activation of collagen promoter in SSc fibroblasts. Imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases might also contribute to the excess accumulation of collagen in the dermis.
authors.affiliation: Department of Dermatology & Plastic Surgery, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8556, Japan. mjin@kumamoto-u.ac.jp
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Jinnin
mesh_terms: D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000473:pathology*; D051785:Smad Proteins / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016207:Cytokines; D051785:Smad Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D003094:Collagen; D017364:Collagenases; D008666:Metalloendopeptidases