1Division of Gastroenterology and Hepatology, Department of MedicineIndiana University School of Medicine Research
2Department of Research, Richard L. Roudebush VA Medical Center
3Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA
4UVM Health Network
5Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
6Department of Nutrition, Texas A&M University, College Station, Texas
7Texas A&M University School of Medicine
Abbreviations: ALT, Alanine aminotransferase; AST, aspartate transaminase; CD, control diet; CD-68, cluster of differentiation 68; CDK4, cyclin dependent kinase 4; Cer, Ceramide; ChIP-PCR, chromatin immunoprecipitation polymerase chain reaction; Co-IP, co-immunoprecipitation; CK-19, cytokeratin 19; CPT1A, carnitine palmitoyl transferase 1A; CPT1B, carnitine palmitoyl transferase 1B; DR, ductular reaction; DGAT2, diacyl glycerol acyl transferase 2; DMSO, Dimethyl Sulfoxide; E2F1, E2 promoter binding transcription factor 1; EIA, enzyme linked immunoassay; FABP1, fatty acid binding protein 1; FCR1, FC epsilon receptor 1 gamma; FFA, free fatty acid; FITC, fluorescein isothiocyanate; FOXO1, Fork-head box transcription factor 1; GAPDH, glyceraldehyde 3 phosphate dehydrogenase; γH2A.X, phosphorylated histone 2A; GPAT3, glyceraldehyde 3 phosphate acyl transferase 3; HFD, high fat diet; H&E, hematoxylin and eosin; HNF4α, hepatocyte nuclear factor 4 alpha; HPC, hepatic progenitor cells; HSC, hepatic stellate cell; IBDM, intrahepatic bile duct mass; IF, immunofluorescence; IGF-1, insulin-like growth factor-1; IGFBP5, insulin like growth factor binding protein 5; IGF1R, insulin like growth factor 1 receptor;IL-6, interleukin-6; IMCL, immortalized murine cholangiocyte cell line; KO, knockout; LW/BW, liver weight/ body weight; MC, mast cell; MCD, methionine-choline deficient; Mdr2-/-, multidrug resistance transporter 2/ ABC transporter B family member 2 knock out; miR/miRNA, micro ribonucleic acid; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; OA, oleic acid/oleate; PA, palmitic acid/palmitate; p16, cyclin-dependent kinase inhibitor 2A; p18, cyclin-dependent kinase 4 inhibitor C; p21, cyclin-dependent kinase inhibitor 1A; PBS, phosphate buffered saline; PSC, primary sclerosing cholangitis; qPCR, quantitative polymerase chain reaction; RNA pol II, RNA polymerase II; Rpb1 NTD, RNA polymerase II subunit 1 N-terminal domain; Rps18, mouse ribosomal protein s18; SA, stearic acid/stearate; SASPs, senescence associated secretory phenotypes; TGF-β1, transforming growth factor beta 1; SIRT1, sirtuin1; TPSβ2, tryptase β2; TUNEL, Terminal deoxynucleotidyl transferase dUTP nick end labeling VM, vivo morpholino; WB, western blot; WT, wild type
This work was supported by the Hickam Endowed Chair, Gastroenterology, Medicine, Indiana University, the Indiana University Health – Indiana University School of Medicine Strategic Research Initiative, the Senior Career Scientist Award (IK6 BX004601) and the VA Merit award (5I01BX000574) to GA and the Career Scientist Award (IK6BX005226) and the VA Merit award (1I01BX003031) to HF, and Career Development Award-2 to LK (1IK2BX005306) from the United States Department of Veteran’s Affairs, Biomedical Laboratory Research and Development Service and NIH grants DK108959 and DK119421 (HF), DK054811, DK115184, DK076898, DK107310, DK110035, DK062975 and AA028711 (GA and SG) and the PSC Partners Seeking a Cure (GA). EG and PO were supported by research funds from Sapienza University of Rome. Portions of these studies were supported by resources at the Richard L. Roudebush VA Medical Center, Indianapolis, IN, and Medical Physiology, Medical Research Building, Temple, TX. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs.
Vik Meadows: Current address Department of Pharmacology and Toxicology, Rutgers University, New Brunswick, NJ
Correspondence Heather Francis, Professor of Medicine, VA Research Career Scientist Scientific Director, Indiana Center for Liver Research Richard L. Roudebush VA Medical Center and Indiana University, Gastroenterology, Medicine 702 Rotary Circle, Rm. 013C, Indianapolis, IN 46202. Email: [email protected]
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