Connective tissue growth factor: an attractive therapeutic target in fibrotic renal disease

Despite diverse initiating insults, glomerulosclerosis and tubulointerstitial fibrosis are pathological features common to most forms of progressive renal disease. Control of systemic hypertension and blockade of the renin-angiotensin system ameliorate the rate of progression of chronic renal disease; however they generally fail to completely arrest the scarring process. While the chain of events leading to scarring are still being defined, TGF-beta is a cytokine that plays a pivotal role in the pathogenesis of glomerulosclerosis and tubulointerstitial fibrosis [1]. Given the pleiotropic effects of TGF-beta, significant attention has focused on the potential of its downstream mediators as therapeutic targets. Connective tissue growth factor (CTGF) is a member of the CCN gene family, which includes CyR61 (cysteine rich 61), Nov (Nephroblastoma overexpressed) and the WISP family (for review see [2,3,4]). These immediate-early genes coordinate complex biologic processes during differentiation and tissue repair [5]. Increased expression of CTGF has been detected in experimental and human renal fibrosis where it correlates with glomerulosclerosis and the degree of tubulointerstitial fibrosis [6]. In these settings CTGF expression is regulated at least in part by TGF-beta. This review details the biology of CTGF with specific reference to its potential as a therapeutic target in renal fibrosis.