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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.

Authors: Ren, F  Shi, H  Zhang, L  Zhang, X  Wen, T  Xie, B  Zheng, S  Chen, Y  Li, L  Chen, D  Duan, Z 
Citation: Ren F, etal., J Viral Hepat. 2016 Jan;23(1):23-31. doi: 10.1111/jvh.12438. Epub 2015 Jul 31.
Pubmed: (View Article at PubMed) PMID:26234401
DOI: Full-text: DOI:10.1111/jvh.12438

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.

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CRRD Object Information
CRRD ID: 32716425
Created: 2020-06-30
Species: All species
Last Modified: 2020-06-30
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.