A Glimpse of the Pathogenetic Mechanisms of Wnt/β-Catenin Signaling in Diabetic Nephropathy

Figure 1

A schematic drawing depicting the role of wnt signaling in diabetic nephropathy. And High glucose induced Ras and GSK-3β activation, which leads to destabilization of β-catenin for degradation and subsequently promotes mesangial cells apoptosis through activation of caspase-3 and PARP. On the other hand, high glucose stimulates some Wnts secretion, increased intracellular Wnts level could activate its receptors FZD and LRP cause to the recruitment of the Dvl and Axin, inhibiting β-catenin phosphorylation and its degradation. Accumulated β-catenin then translocates to the nucleus and regulates the transcription activity of target genes such as Snail, a-SMA by TCF and CBP. In mesangial cell, the stabilized β-catenin induces fibronectin and α-SMA expression, which is suggested to be involved in epithelial-mesenchyml phenotypic transition (EMT) and contributes to kidney fibrosis under DN condition. In podocyte, it induced the Snail and suppressed nephrin expression, leading to podocyte EMT and dysfunction eventually leads to proteinuria and kidney fibrosis. In addition, high glucose activation of Wnt/β-catenin induces EMT formation and fibrosis in tubular cells by increased Snail and Twist expression. All of them eventually cause renal and tubular intestinal fibrosis in DN.