title: The dysregulation of endoplasmic reticulum stress response in acute-on-chronic liver failure patients caused by acute exacerbation of chronic hepatitis B.
abstract: Although endoplasmic reticulum (ER) stress is critical in various liver diseases, its role in acute-on-chronic liver failure (AoCLF) caused by acute exacerbation of chronic hepatitis B (CHB) is still elusive. This study aimed to analyse ER stress responses in the progression of HBV-related AoCLF. Normal liver tissues (n = 10), liver tissues of CHB (n = 12) and HBV-related patients with AoCLF (n = 19) were used. Electron microscopy of the ultrastructure of the ER was carried out on liver specimens. The gene and protein expression levels of ER stress-related genes were measured. We further analysed the correlation between the expression levels of ER stress-related molecules and liver injury. Electron microscopy identified typical features of the ER microstructure in AoCLF subjects. Among the three pathways of unfolded protein responses, the PKR-like ER kinase and inositol-requiring enzyme 1 signalling pathway were activated in CHB subjects and inactivated in AoCLF subjects, while the activating transcription factor 6 signalling pathway was sustained in the activated form during the progression of AoCLF; the expression of glucose-regulated protein (Grp)78 and Grp94 was gradually decreased in AoCLF subjects compared to healthy individuals and CHB subjects, showing a negative correlation with serum ALT, AST and TBIL; moreover, the ER stress-related apoptosis molecules were activated in the progression of acute exacerbation of CHB. The dysregulated ER stress response may play a complicated role in the pathogenesis of AoCLF, and a severe ER stress response may predict the occurrence of AoCLF caused by acute exacerbation of CHB.
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: F
authors.initials: F
authors.lastname: Ren
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: T
authors.initials: T
authors.lastname: Wen
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Xie
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: S
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.affiliation: Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Duan
mesh_terms: D051702:Activating Transcription Factor 6 / Q000096:biosynthesis; D065290:Acute-On-Chronic Liver Failure / Q000473:pathology* / Q000821:virology; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D004722:Endoribonucleases / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000473:pathology* / Q000821:virology; D006801:Humans; D008099:Liver / Q000473:pathology* / Q000821:virology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D056811:Unfolded Protein Response / Q000502:physiology; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; C053387:endoplasmin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C460640:EIF2AK3 protein, human; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D004722:Endoribonucleases; D001663:Bilirubin
keywords: acute-on-chronic liver failure; chronic hepatitis B; endoplasmic reticulum stress; hepatitis B virus; unfolded protein response