Unveiling hepatic Kruppel-like factor 15 as the key regulator of cyclosporine A metabolism and adverse effects.

ABSTRACT: Cyclosporine A (CsA) is a widely used immunosuppressant for posttransplantation and autoimmune diseases, but its clinical application is limited by severe hepatorenal toxicity. Krüppel-like factor 15 (KLF15), a key regulator of xenobiotic metabolism, has been shown to modulate the metabolism of acetaminophen and rifampicin and play a role in the associated drug-induced liver toxicity. However, its role in CsA metabolism and CsA-induced hepatorenal injury remains unclear. This study aimed to investigate whether hepatic KLF15 regulates CsA metabolism and serves as a potential therapeutic target for mitigating CsA-induced hepatorenal toxicity. KLF15 broadly suppressed the CsA detoxification pathways by inhibiting key metabolic enzymes and transporters. Inhibition of hepatic KLF15 enhanced CsA

SUBMITTER: Guo X 

PROVIDER: S-EPMC12597601 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature