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


RESULTS
Emerging evidence from in-vitro studies of renal cells indicates that connective tissue growth factor is a crucial mediator for transforming growth factor-beta-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-beta is stronger than first thought. While transforming growth factor-beta induces the expression of connective tissue growth factor, the latter plays a key role in both bioactivation of latent transforming growth factor-beta and the promotion of its Smad signalling activity.


CONCLUSIONS
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-beta. 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-beta. Because of the inflammatory and immunosuppressive properties of transforming growth factor-beta, connective tissue growth factor seems to be an attractive alternative therapeutic target for combating renal fibrosis.
Abdel Wahab
Nadia
N
Cell and Molecular Biology Section, Division of Biomedical Sciences, Faculty of Medicine, Imperial College London, London, England, UK. nadia.wahab@imperial.ac.uk
Mason
Roger M
RM
D000818:Animals; D055513:Connective Tissue Growth Factor; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000502:physiology*; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor