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
Affiliations
Seul Lee
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea
Dong-Cheol Woo
Convergence medicine research center, Asan Institute for Life Sciences, Asan Medical Center, and Department of Convergence Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea
Jeeheon Kang
Center for Bio-Imaging of New Drug Development, Asan Life Science Institution, Asan Medical Centre, Seoul 05505, Korea
Moonjin Ra
Hongcheon Institute of Medicinal Herb, 101 Yeonbongri, Hongcheon 25142, Korea
Ki Hyun Kim
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea
Seoung Rak Lee
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea
Dong Kyu Choi
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea
Heejin Lee
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea
Ki Bum Hong
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea
Sang-Hyun Min
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea
Yongjun Lee
Hongcheon Institute of Medicinal Herb, 101 Yeonbongri, Hongcheon 25142, Korea
Ji Hoon Yu
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea
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.
