Activation of TGF-β/Smad pathway signalling also induces supra-regulation of connective tissue growth factor (CTGF) and of vascular endothelium growth factor (VEGF), and both act by paracrine mechanisms on mesangial cells, stimulating the synthesis of ECM proteins and, later, inducing glomerulosclerosis and progressive renal fibrosis [26]. This evidence concerns the gene CCN2 and glomerulosclerosis.