Connective tissue growth factor: potential role in glomerulosclerosis and tubulointerstitial fibrosis.
Transforming growth factor beta (TGF-beta) is a pivotal driver of glomerulosclerosis and tubulointerstitial fibrosis in renal diseases. Because TGF-beta also plays important anti-inflammatory and antiproliferative roles in mammalian systems, there has been a recent drive to elucidate downstream mediators of TGF-beta's pro-fibrotic effects with the ultimate goal of developing new anti-fibrotic strategies for treatment of chronic diseases. Connective tissue growth factor (CTGF) belongs to the CCN family of immediate early response genes. Several lines of evidence suggest that CTGF is an important pro-fibrotic molecule in renal disease and that CTGF contributes to TGF-beta bioactivity in this setting. CTGF expression is increased in the glomeruli and tubulointerstium in a variety of renal disease in association with scarring and sclerosis of renal parenchyma. In model systems in vitro, mesangial cell CTGF expression is induced by high extracellular glucose, cyclic mechanical strain and TGF-beta. Recombinant human CTGF augments the production of fibronectin and type IV collagen by mesangial cells and the effects of high glucose on mesangial cell CTGF expression and matrix production are attenuated, in part, by anti-TGF-beta antibody. In aggregate, these observations identify CTGF as an attractive therapeutic target in fibrotic renal diseases.
Gupta
S
S
Department of Medicine and Therapeutics, Mater Misericordiae Hospital, University College Dublin, Dublin, Ireland.
Clarkson
M R
MR
Duggan
J
J
Brady
H R
HR
D055513:Connective Tissue Growth Factor; D005923:Glomerulosclerosis, Focal Segmental / Q000503:physiopathology*; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D009395:Nephritis, Interstitial / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000502:physiology
C526317:CCN2 protein, human; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor