Connective tissue growth factor and renal diseases: some answers, more questions

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Abstract
Connective tissue growth factor (CCN2) has recently received much attention as a possible key determinant of progressive renal fibrosis. However, the mechanism(s) by which this growth factor functions is not known. The purpose of this review is to summarize and discuss the recent findings regarding the possible mechanisms involved. Emerging evidence from in-vitro studies of renal cells indicates that connective tissue growth factor is a crucial mediator for transforming growth factor-β-induced cellular dysfunction, manifest by increased cellular hypertrophy, synthesis of extracellular matrix proteins and their deposition and assembly around the cells. Indeed, recent evidence suggests that the interrelationship between connective tissue growth factor and transforming growth factor-β is stronger than first thought. While transforming growth factor-β induces the expression of connective tissue growth factor, the latter plays a key role in both bioactivation of latent transforming growth factor-β and the promotion of its Smad signalling activity. Connective tissue growth factor is clearly implicated in the pathogenesis of progressive renal disease. Although there is much to learn about the production, function, and mechanism of action of connective tissue growth factor, some progress has been made in understanding the molecular basis of its relationship with transforming growth factor-β. Elucidating the signal transduction pathways activated by connective tissue growth factor will also definitely help to clarify other actions of connective tissue growth factor which may be independent of transforming growth factor-β. Because of the inflammatory and immunosuppressive properties of transforming growth factor-β, connective tissue growth factor seems to be an attractive alternative therapeutic target for combating renal fibrosis.