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Connective tissue growth factor: A new and important player in the pathogenesis of fibrosis

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Abstract

Connective tissue fibrosis is the final common pathogenic process for almost all forms of chronic tissue injury. Whether caused by vascular dysfunction, inflammation, metabolic injury, trauma, or environmental agents, once initiated the fibrogenic process results in the progressive replacement of the normal tissue architecture with fibrotic lesions that eventually lead to organ compromise and failure. Fibrosis can be considered as a dysregulation in the normal tissue repair mechanism, resulting in severe tissue scarring. Fibrosis appears to be a consequence of linked processes, including the proliferation of resident fibroblast cell types, the increased production and deposition of extracellular matrix components, and the transition of fibroblasts into cells exhibiting a myofibroblast phenotype. Although transforming growth factor-beta (TGFβ) has long been regarded as a pivotal growth factor in the formation and maintenance of connective tissues and as a major driving influence in many progressive fibrotic diseases, attention has focused recently on the role of connective tissue growth factor (CTGF) in fibrosis. CTGF is selectively and rapidly induced in mesenchymally derived cells by the action of TGFβ. CTGF expression is increased in many fibrosing diseases. In addition, increasing evidence from in vivo and in vitro models of tissue remodeling and fibrosis suggest that CTGF may represent a downstream effector molecule of the profibrotic activities of TGFβ in the maintenance and repair of connective tissues and within fibrotic disease settings.

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Leask, A., Holmes, A. & Abraham, D.J. Connective tissue growth factor: A new and important player in the pathogenesis of fibrosis. Curr Rheumatol Rep 4, 136–142 (2002). https://doi.org/10.1007/s11926-002-0009-x

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