DUSP26 protects against acute kidney injury by dephosphorylating p53 at serine 312

Acute kidney injury (AKI) remains a leading cause of morbidity and mortality, yet the molecular pathways driving kidney tubule damage in AKI are not fully understood. Here, we report dual-specificity phosphatase 26 (DUSP26) as a critical regulator of kidney tubule injury in AKI. In our study, DUSP26 expression was markedly reduced in kidney biopsies from AKI patients and in murine models of cisplatin nephrotoxic and ischemic AKI. This down-regulation was driven by hypermethylation of the gene promoter of DUSP26 in kidney tubular cells. Loss of DUSP26 exacerbated tubular damage, whereas knock-in of DUSP26 specifically in kidney proximal tubule cells conferred protection.