Further investigation in this area is essential for the application of p53 as therapeutic target to prevent and treat AKI or impede its progression to CKD.
SIRT1 activation and p53 deacetylation might be identified as potential targets for attenuating premature renal senescence and retarding the progression of CKD post AKI.
We demonstrate a senescence phenotype in the AVF-CKD model, as indicated by increased expression of p16<sup>Ink4a</sup>, p21<sup>Cip1</sup>, and p53 and expected changes for certain senescence-associated microRNAs.
Treatment with a p53 inhibitor following IRI resulted in not only decreased expression of G1 arrest markers but also decreased fibrosis, suggesting that prolonged epithelial G1 cell cycle arrest might be partially responsible for impaired recovery from superimposed AKI on CKD.
Further, it promotes the expression of p53 by ROS-induced activation of nuclear factor kappa B, thereby accelerating senescence of proximal tubular cells with progression of CKD.
The unique TP53 mutational signature for AA identified in this study can be used to explore the hypothesis that botanical products containing this human carcinogen and nephrotoxin are responsible, in part, for the high prevalence of UUC and chronic renal disease in countries where Aristolochia herbal remedies traditionally have been used for medicinal purposes.