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World J Gastroenterol. Nov 21, 2017; 23(43): 7657-7665
Published online Nov 21, 2017. doi: 10.3748/wjg.v23.i43.7657
Functional interaction of endoplasmic reticulum stress and hepatitis B virus in the pathogenesis of liver diseases
So Young Kim, Yi Yi Kyaw, Jaehun Cheong
So Young Kim, Yi Yi Kyaw, Jaehun Cheong, Department of Molecular Biology, Pusan National University, Busan 609-735, South Korea
Author contributions: Kim SY and Kyaw YY prepared the manuscript; Cheong J designed and revised the manuscript.
Supported by the National Research Foundation of South Korea, No. NRF-2009-0093195; and Basic Science Research Program through the NRF funded by the Ministry of Education, No. NRF-2013R1A1A2057634.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jaehun Cheong, PhD, Department of Molecular Biology, Pusan National University, Busan 609-735, South Korea. molecule85@pusan.ac.kr
Telephone: +82-51-5102277 Fax: +82-51-5139258
Received: April 21, 2017
Peer-review started: April 25, 2017
First decision: June 22, 2017
Revised: September 1, 2017
Accepted: November 1, 2017
Article in press: November 1, 2017
Published online: November 21, 2017
Abstract

Hepatitis B virus (HBV) is a non-cytopathic virus that causes acute and chronic inflammatory liver diseases, often leading to the pathogenesis of hepatocellular carcinoma (HCC). Although many studies for the roles of HBV on pathogenesis of the liver diseases, such as non-alcoholic fatty liver disease (NAFLD), hepatic inflammation, cirrhosis, and HCC, have been reported, the mechanisms are not fully understood. Endoplasmic reticulum (ER) and mitochondria have the protective mechanisms to restore their damaged function by intrinsic or extrinsic stresses, but their chronic dysfunctions are associated with the pathogenesis of the various diseases. Furthermore, HBV can affect intra- or extracellular homeostasis through induction of ER and mitochondrial dysfunctions, leading to liver injury. Therefore, the mechanism by which HBV induces ER or mitochondrial stresses may be a therapeutic target for treatment of liver diseases.

Keywords: Liver disease, Hepatitis B virus, Hepatitis B virus X protein, Endoplasmic reticulum stress, Unfolded protein response

Core tip: Endoplasmic reticulum (ER) is the major site of protein folding and calcium storage. Beside the role of ER in protein homeostasis, it controls the cholesterol production and lipid-membrane biosynthesis as well as surviving and cell death signaling mechanisms in the cell. It is well-documented that abnormal metabolic regulation induces adverse effects in liver disorders, such as non-alcoholic steatosis hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma which are associated with hepatitis B virus (HBV) infection. Recent animal model and human studies have showed ER stress as an emerging factors involved in the development of metabolic and liver diseases. In this review, we will summarize the crucial effects of ER stress response in the pathogenesis of HBV-induced liver diseases.