Connective tissue growth factor induces tubular epithelial to mesenchymal transition through the activation of canonical Wnt signaling in vitro

AbstractBackground: Overwhelming evidences suggest epithelial to mesenchymal transition (EMT) of tubular epithelial cells contributes to renal fibrosis of chronic kidney disease (CKD). Connective tissue growth factor (CTGF) plays an important role in the pathogenesis of EMT. However, the molecular mechanisms that regulate cell behaviors are not clear. Objective: The purpose of this study was to investigate whether CTGF induces EMT via activation of canonical Wnt signaling in renal tubular epithelial cells. Methods: Human renal proximal tubular epithelial cells (HK-2) were divided into control group, CTGF group and dickkopf (Dkk)-1 plus CTGF group. We assessed the biological changes of canonical Wnt signaling, including phosphorylation of low-density lipoprotein receptor-related protein (LRP6) and glycogen synthase kinase-3β (GSK-3β) and accumulation and nuclear localization of β-catenin. Meanwhile, morphological changes of the three groups were observed and tubular EMT was further confirmed by detecting t...