NNMT/1-MNA protects against hepatic ischemia-reperfusion injury through the AKT/FOXO1/ANGPT2/JNK axis

May 22, 2025Nature communications

NNMT and 1-MNA protect the liver from blood flow injury through a cell survival and stress response pathway

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Abstract

A decrease in hepatic expression and serum 1-MNA levels is observed during .

  • Nicotinamide N-methyltransferase (NNMT) is involved in the conversion of nicotinamide to N-methylnicotinamide (1-MNA).
  • NNMT overexpression and treatment with exogenous 1-MNA may reduce the severity of hepatic ischemia-reperfusion injury (HIRI) in male mice and liver cell models.
  • NNMT and 1-MNA are associated with inflammation, cell death, and blood vessel damage during HIRI through the AKT/FOXO1//JNK signaling pathway.
  • Depleting NNMT in the liver is linked to increased levels of ANGPT2 and worsened HIRI, which can be improved by knocking down ANGPT2.
  • NNMT/1-MNA/ANGPT2 may play regulatory roles in HIRI through the JNK signaling pathway.

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