TB Research

Inhibition of YAP can down-regulate NLRP3 inflammasome and improve anti-tuberculosis drug-induced liver injury

Long Y, Li X, Liu Y, Zhang M, Feng F

Xenobiotica; the fate of foreign compounds in biological systems · 2025-02

Abstract

Yes-associated protein (YAP) is a core effector molecule in the Hippo signalling pathway, but its role in antituberculosis drug-induced liver injury (ADLI) is unclear. We aimed to explore the regulatory effects of YAP on the NLRP3 inflammasome in ADLI and its potential hepatoprotective effects.An ADLI animal model was established. Various indicators of experimental animals were detected at 0, 7, 14, and 21 days. On day 7, HE staining observed liver tissue, and liver index, ALT, and AST levels confirmed the ADLI model. YAP's mRNA and protein levels were examined, YAP inhibitor effects were observed, and NLRP3 inflammasome, inflammation, and oxidative stress indicators were analysed.It was found that the mRNA and protein levels of YAP increased during ADLI and then decreased due to the action of YAP inhibitors. YAP caused an elevation in NLRP3 inflammasome indicators, as well as increased expression of inflammation and oxidative stress. After feeding with YAP inhibitors, these indicators were reduced.The results suggest that targeting YAP may be a novel therapeutic strategy for alleviating antituberculosis drug-induced liver injury.

MeSH terms

  • Liver
  • Animals
  • Adaptor Proteins, Signal Transducing
  • Antitubercular Agents
  • Down-Regulation
  • Oxidative Stress
  • Male
  • Inflammasomes
  • Chemical and Drug Induced Liver Injury
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • YAP-Signaling Proteins