Connective tissue growth factor: growth factor, matricellular organizer, fibrotic biomarker or molecular target for anti-fibrotic therapy in SSc

SSc is characterized by enhanced extracellular matrix (ECM) production resulting in excessive scarring and replacement fibrosis affecting the interstitial and vascular compartments of multiple organs. Although the precise molecular mechanisms driving fibrosis remain elusive, TGF-beta and connective tissue growth factor (CTGF), are considered key mediators. CTGF is over-expressed in lesional tissue and enhanced levels in the circulation are an indicator of disease extent and severity. Rapidly induced by TGF-beta and ET-1, CTGF activates several signal transduction pathways via surface receptors that modulate the functional activities of fibroblasts, endothelial and smooth muscle cells. In vivo, over-expression of CTGF causes ECM accumulation and promotes tissue fibrosis. In animal models of SSc, neutralization of CTGF with antibody blockade or siRNA, suppresses fibrogenesis. This article examines the role of CTGF as an integrator of extracellular signals, fibrotic biomarker and discusses the potential value of CTGF antagonism as a therapeutic strategy in SSc.