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The dysregulation of endoplasmic reticulum stress response in acute‐on‐chronic liver failure patients caused by acute exacerbation of chronic hepatitis B
Author(s) -
Ren F.,
Shi H.,
Zhang L.,
Zhang X.,
Wen T.,
Xie B.,
Zheng S.,
Chen Y.,
Li L.,
Chen D.,
Duan Z.
Publication year - 2016
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12438
Subject(s) - endoplasmic reticulum , exacerbation , medicine , unfolded protein response , chronic hepatitis , acute hepatitis , liver failure , immunology , hepatitis , biology , microbiology and biotechnology , virus
Summary Although endoplasmic reticulum ( ER ) stress is critical in various liver diseases, its role in acute‐on‐chronic liver failure (Ao CLF ) 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 Ao CLF . Normal liver tissues ( n = 10), liver tissues of CHB ( n = 12) and HBV ‐related patients with Ao CLF ( 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 Ao CLF 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 Ao CLF subjects, while the activating transcription factor 6 signalling pathway was sustained in the activated form during the progression of Ao CLF ; the expression of glucose‐regulated protein (Grp)78 and Grp94 was gradually decreased in Ao CLF 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 Ao CLF , and a severe ER stress response may predict the occurrence of Ao CLF caused by acute exacerbation of CHB .