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31 TGF-β and Fibrosis

Erwin P. Böttinger


Fibrosis is a cardinal feature of most chronic degenerative diseases and may affect virtually every tissue and organ system. The fibrotic response has been characterized as inappropriate repair by connective tissue resulting in scarring, associated with loss of normal tissue architecture and function. The degeneration of functional cell types and accumulation of mesenchymal cells and extracellular matrix (ECM) typically progress slowly over several years, resulting eventually in organ failure. Fibrotic conditions, irrespective of their diverse etiology, anatomic location, and natural history, share common pathogenetic features: excessive secretion and activation of profibrotic cytokines, influx of inflammatory cells, loss of differentiated epithelial cells, expansion and activation of fibroblastoid cells, and ECM synthesis and organization (Border and Noble 1994; Friedman 2003). Because these features are also observed in normal wound healing, it has been proposed that fibrosis can be conceptualized as “healing without end” or “the dark side of tissue repair” (Border and Noble 1994).

Disease-oriented studies in experimental models and human disease universally demonstrate alterations of transforming growth factor-β (TGF-β) expression in tissues affected by fibrosis, including pulmonary fibrosis (Hoyt and Lazo 1989; Raghu et al. 1989), hepatic fibrosis (Czaja et al. 1989; Nakatsukasa et al. 1990), renal fibrosis (Border et al. 1990a; Okuda et al. 1990; Coimbra et al. 1991; Jones et al. 1991), ocular fibrosis (Connor et al. 1989), cardiac fibrosis (Chua et al. 1991), radiation fibrosis (Anscher et al. 1990), and systemic sclerosis and fibrotic skin diseases (Peltonen et al. 1990; Falanga and Julien 1990). TGF-β is the prototypical...

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