Solving the puzzle of fibrosis resolution in alcohol-associated liver disease, an insight from KDM5 demethylases and LXR activation

1Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 2Roudebush Veterans Administration Medical Center, Indianapolis, IN Running title: Genomic studies in AUD and ALD. Abbreviations: ABCG1, ATP binding cassette subfamily G member 1; ACC, Acetyl-CoA carboxylase; AH, Alcohol-associated hepatitis; AhR, Aryl hydrocarbon receptor; ALD, Alcohol-associated liver disease; AP-1, Activator protein 1; CCl4, Carbon tetrachloride; COL3a1, Collagen type III alpha 1 chain; CYP27A1, Cytochrome P450 family 27 subfamily A member 1; ECM, Extracellular matrix; FAS, Fatty acid synthase; GABARAPL1, GABA type A receptor associated protein like 1; GADD45, Growth arrest and DNA damage inducible 45; HNF4a:Hepatocyte nuclear factor 4 alpha; HSC, Hepatic stellate cells; ITGAV, Integrin subunit alpha V; KDM5, Lysine demethylase 5; LSDs, Lysine-specific demethylases; LXRs, Liver X receptors; MMPs, Matrix-degrading metalloproteinases; NF-κB, Nuclear factor kappa B; NPCs, Nonparenchymal cells; PPARγ, Peroxisome proliferator-activated receptor gamma; SCD1, Stearoyl-CoA desaturase 1; SMAD, Suppressor of mothers against decapentaplegic; SREBP, Sterol regulatory element-binding protein 1C; STAT-1, Signal transducer and activator of transcription 1; TGF-β, Transforming growth factor β; TIMPs, Tissue inhibitors of metalloproteinases; αSMA, α-Smooth muscle actin. Correspondence Jing Ma, 702 Rotary Circle, Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Email: [email protected]