The role of the histone methyltransferase ezh2 in liver inflammation and fibrosis in stam nash mice

Seul Lee, Dong Cheol Woo, Jeeheon Kang, Moonjin Ra, Ki Hyun Kim, Seoung Rak Lee, Dong Kyu Choi, Heejin Lee, Ki Bum Hong, Sang Hyun Min, Yongjun Lee, Ji Hoon Yu

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a leading form of chronic liver disease, with few biomarkers and treatment options currently available. Non-alcoholic steatohepatitis (NASH), a progressive disease of NAFLD, may lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Epigenetic modification can contribute to the progression of NAFLD causing non-alcoholic steatohepatitis (NASH), in which the exact role of epigenetics remains poorly understood. To identify potential therapeutics for NASH, we tested small-molecule inhibitors of the epigenetic target histone methyltransferase EZH2, Tazemetostat (EPZ-6438), and UNC1999 in STAM NASH mice. The results demonstrate that treatment with EZH2 inhibitors decreased serum TNF-alpha in NASH. In this study, we investigated that inhibition of EZH2 reduced mRNA expression of inflammatory cytokines and fibrosis markers in NASH mice. In conclusion, these results suggest that EZH2 may present a promising therapeutic target in the treatment of NASH.

Original languageEnglish
Article number93
JournalBiology
Volume9
Issue number5
DOIs
StatePublished - 2020

Keywords

  • EZH2
  • Enhancer of zeste homolog 2
  • H3K27me3
  • Histone methyltransferase (HMT)
  • Trimethylation on Lys 27 of histone H3

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