title: Dysplastic hepatocytes develop nuclear inclusions in a mouse model of viral hepatitis.
abstract: Viral hepatitis resulting in chronic liver disease is an important clinical challenge and insight into the cellular processes that drive pathogenesis will be critical in order to develop new diagnostic and therapeutic options. Nuclear inclusions in viral and non-viral hepatitis are well documented and have diagnostic significance in some disease contexts. However, the origins and functional consequences of these nuclear inclusions remain elusive. To date the clinical observation of nuclear inclusions in viral and non-viral hepatitis has not been explored at depth in murine models of liver disease. Herein, we report that in a transgenic model of hepatitis B surface antigen mediated hepatitis, murine hepatocytes exhibit nuclear inclusions. Cells bearing nuclear inclusions were more likely to express markers of cell proliferation. We also established a correlation between these inclusions and oxidative stress. N-acetyl cysteine treatment effectively reduced oxidative stress levels, relieved endoplasmic reticulum (ER) stress, and the number of nuclear inclusions we observed in the transgenic mice. Our results suggest that the presence of nuclear inclusions in hepatocytes correlates with oxidative stress and cellular proliferation in a model of antigen mediated hepatitis.
authors.affiliation: Section of Gastroenterology/Hepatology, Department of Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Thakur
authors.affiliation: Department of Pharmacology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America; Department of Ophthalmology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Folami
authors.initials: F
authors.lastname: Lamoke
authors.affiliation: Department of Pathology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Chaffin
authors.affiliation: Department of Pharmacology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America; Department of Ophthalmology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Manuela
authors.initials: M
authors.lastname: Bartoli
authors.affiliation: Department of Pathology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America; Georgia Regents University Cancer Center, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America; Charlie Norwood Veterans Affairs Medical Center, Augusta, Georgia, United States of America.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Lee
authors.affiliation: Section of Gastroenterology/Hepatology, Department of Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America; Georgia Regents University Cancer Center, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Duncan
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism; D053145:Cell Nucleus Size; D016922:Cellular Senescence; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006505:Hepatitis / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D045586:Intranuclear Inclusion Bodies / Q000473:pathology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018384:Oxidative Stress; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism
chemical_list: D000447:Aldehydes; D015415:Biomarkers; D006514:Hepatitis B Surface Antigens; D018809:Proliferating Cell Nuclear Antigen; D006003:Glycogen; C027576:4-hydroxy-2-nonenal