Modulation of Collagen Gene Expression: Its Relation to Fibrosis in Systemic Sclerosis and Other Disorders

Fibrosis is the pathologic hallmark of many common diseases. Much information has recently emerged about the cellular and biochemical events that result in its development and progression. It is now known that in affected tissues, chronic inflammation generally precedes fibrosis and that inflammatory cell-derived cytokines are crucial mediators of fibrogenesis. Several cytokines have been identified that influence wound healing and tissue repair processes in vivo and that modulate the production of collagen in vitro. Of these, transforming growth factor-β is of the most interest because this pleiotropic cytokine is expressed at high levels during tissue remodeling and greatly affects the formation of connective tissue. Furthermore, it has been recently shown that transforming growth factor-β can stimulate the transcription of collagen genes through the production or activation of specific DNA-binding trans-acting factors. A precise understanding of the molecular mechanisms responsible for the effects of this cytokine on collagen gene expression may allow the design of selective therapeutic interventions aimed at retarding or preventing the development of fibrosis.