Fig. 11. Proposed mechanisms by which PXR alleviates kidney fibrosis through interacting with p53.

Fibrotic kidney exhibits increased expression of p53, which promotes the assembly of the p53/p-Smad3 complex to induce profibrotic gene expression. In addition, p53 can bind to the promoter region of Wnt7a to increase Wnt7a transcription and β-catenin activation, leading to increased expression of the downstream profibrotic genes. By physically interacting with p53, PXR reduces the binding of p53 to p-Smad3 protein and Wnt7a gene promoter to suppress both the p-Smad3 and β-catenin signaling, thereby attenuating renal fibrosis. Fzd Frizzled, LRP5/6 low density lipoprotein receptor related protein-5 or −6, PRR prorenin receptor, CBP cAMP response element binding protein (CREB)-binding protein, TCF T-cell factor, LEF lymphoid enhancer-binding factor.