Inhibition of Mettl3 alleviates low-dose cisplatin-induced renal fibrosis and enhances the chemotherapeutic efficacy in mouse models of cancer.

ABSTRACT: Cisplatin (CDDP), a commonly utilized anti-tumor drug, leads to acute kidney injury (AKI) and chronic kidney disease (CKD). The mechanisms and therapeutic approaches for injury in AKI have been extensively studied, but the mechanisms resulting in CKD are poorly comprehended and intervention methods are scarce. In the current study, we found that under different phases of the repeated low-dose CDDP treatment, Mettl3 expression was induced by two different mechanisms. In the presence of CDDP, the transcription factor Hif1-α was induced, resulting in an increase in Mettl3. When CDDP was removed, the previously increased Mettl3 caused an elevated lactate level, which formed a positive feedback loop by mutually reinforcing each other's expression via H3K18 lactylation. Functionally, we disclose

SUBMITTER: Xie Y 

PROVIDER: S-EPMC12320029 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature