Abstract
TP53 is a gene with complicated functions, which is involved in maintaining genomic stability and regulating biological processes such as apoptosis, senescence, and cell-cycle arrest. In recent years, p53 isoforms have been comprehensively investigated in multiple cancer types including melanoma, ovarian cancer, lung cancer, among others. However, the roles of p53 isoforms in kidney injury and repair remain elusive. The latest research progress indicates that p53alpha is involved in the occurrence of acute kidney injury and the subsequent kidney repair process mainly by regulating apoptosis, cell cycle arrest, and autophagy. Studies have shown that the p53 isoform delta133p53alpha primarily functions to inhibit apoptosis and facilitate DNA double-strand break repair as well as impacts the transcriptional activity of p53alpha via forming hetero-oligomeric complex. These processes may play a pivotal role in the repair of kidney injury. However, the specific mechanisms by which delta133p53alpha acts in the process of kidney injury and repair remain unclear. Moreover, pharmacological inhibition of p53alpha (e.g. pifithrin-alpha) attenuates G2/M arrest, while proximal tubule-specific TP53 knockout confers protection against ischemia-reperfusion injury. Given the diverse and extensive functions of p53 isoforms, this review aims to explore the novel therapeutic potential of p53 isoforms in kidney injury and repair treatment.