Figure 5. Interaction of Wnt/β-catenin signaling pathway with p53 in AKI and CKD.

In the AKI model, the Wnt/β-catenin signaling pathway is transiently activated, and activated β-catenin can protect the kidney from apoptosis by inhibiting p53 expression or inhibiting p53 activity. In the CKD model, p53 can increase the expression of Wnt ligands through transcriptional regulation, thereby inducing the continuous activation of the Wnt/β-catenin signaling pathway, which leads to the dissociation of the destruction complex composed of axin, CK1, Dvl, APC, and GSK3β, and finally leads to the accumulation of β-catenin in the cytoplasm. The accumulated β-catenin enters the nucleus and promotes renal fibrosis by regulating the transcription of target genes. In addition, the accumulation of β-catenin may also increase the expression of p53, thereby inducing apoptosis and aggravating kidney damage in the process of CKD.

AKI, acute kidney injury; APC, adenomatous polyposis coli; CBP, cyclic adenosine monophosphate response-element binding protein; CKD, chronic kidney disease; CK1, casein kinase 1; Dvl, dishevelled; FZD, frizzled protein; GSK3β, glycogen synthase kinase 3β; LEF, lymphoid enhancer binding factor; PRR, pattern recognition receptor; TCF, T-cell factor.