CCN2 and renal fibrosis: Studies have shown that the AGE/RAGE signaling pathway can promote the expression of NF-κB [46], up-regulate TGF-β1, VEGF [47], activate NADPH oxidases, induce the expression and release of inflammatory factors and adhesion factors, increase vascular permeability, increase the expression of connective tissue growth factor, and enhance oxidative stress, thus increasing proteinuria, promoting renal fibrosis, leading to DN onset and development.