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lüll Insights into the molecular mechanism of chronic fibrosis: the role of connective tissue growth factor in scleroderma Leask A; Denton CP; Abraham DJJ Invest Dermatol 2004[Jan]; 122 (1): 1-6Connective tissue growth factor (CCN2), a member of the CCN family of proteins, is a cysteine-rich matricellular protein. Connective tissue growth factor is not normally expressed in dermal fibroblasts unless induced. The most potent inducer of connective tissue growth factor thus far identified is transforming growth factor beta. Connective tissue growth factor, however, is constitutively overexpressed by fibroblasts present in skin fibrotic lesions, including scleroderma. The overexpression of connective tissue growth factor present in fibrotic lesions contributes to the phenotype of scleroderma in that connective tissue growth factor promotes matrix deposition, and fibroblast adhesion and proliferation. In animal models, whereas either transforming growth factor beta or connective tissue growth factor alone produce only a transient fibrotic response, connective tissue growth factor and transforming growth factor beta act together to promote sustained fibrosis. Thus the constitutive overexpression of connective tissue growth factor by fibroblasts present in fibrotic lesions would be expected to contribute directly to chronic, persistent fibrosis. This review discusses recent information regarding insights into connective tissue growth factor biology and, using scleroderma as a model system, the part connective tissue growth factor might play in fibrotic disease.|Animals[MESH]|Chronic Disease[MESH]|Connective Tissue Growth Factor[MESH]|Connective Tissue/*physiopathology[MESH]|Gene Expression[MESH]|Humans[MESH]|Immediate-Early Proteins/*genetics[MESH]|Intercellular Signaling Peptides and Proteins/*genetics[MESH]|Scleroderma, Systemic/*pathology/*physiopathology[MESH] |