title: Transcriptional profiling of the scleroderma fibroblast reveals a potential role for connective tissue growth factor (CTGF) in pathological fibrosis.
abstract: The cause of fibrotic disease is unknown. We have undertaken transcriptional profiling of dermal fibroblasts cultured from patients with the fibrotic disease scleroderma (systemic sclerosis, SSc) to identify genes overexpressed in fibrosis and have explored their contribution to the fibrotic phenotype. Connective tissue growth factor (CTGF, CCN2), a member of the CCN family of proteins, is overexpressed in SSc fibroblasts. In adult skin, CTGF is not normally expressed in dermal fibroblasts. However, CTGF is induced during the wound healing response and is constitutively overexpressed by fibroblasts present in fibrotic lesions. The overexpression of CTGF present in fibrotic lesions contributes to the phenotype of scleroderma in that CTGF promotes matrix deposition, and fibroblast adhesion and proliferation. In animal models, whereas either TGF beta or CTGF alone produce only a transient fibrotic response, CTGF and TGF beta act together to promote sustained fibrosis. Thus the constitutive overexpression of CTGF by fibroblasts present in fibrotic lesions would be expected to directly contribute to chronic, persistent fibrosis.
authors.affiliation: Centre for Rheumatology, Royal Free and University College Medical School, University College London, London, UK. a.leask@rfc.ucl.acuk
authors.forename: Andrew
authors.initials: A
authors.lastname: Leask
mesh_terms: D000818:Animals; D055513:Connective Tissue Growth Factor; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D010641:Phenotype; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism*; D020218:Response Elements; D012595:Scleroderma, Systemic / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor