Targeting endoplasmic reticulum stress in liver disease.
BACKGROUND
The accumulation of unfolded protein in the endoplasmic reticulum (ER) initiates an unfolded protein response (UPR) via three signal transduction cascades, which involve protein kinase RNA-like ER kinase (PERK), inositol requiring enzyme-1α (IRE1α) and activating transcription factor-6α (ATF6α). An ER stress response is observed in nearly all physiologies related to acute and chronic liver disease and therapeutic targeting of the mechanisms implicated in UPR signaling have attracted considerable attention.


METHODS
This review focuses on the correlation between ER stress and liver disease and the possible targets which may drive the potential for novel therapeutic intervention. Expert Commentary: We describe pathways which are involved in UPR signaling and their potential correlation with various liver diseases and underlying mechanisms which may present opportunities for novel therapeutic strategies are discussed.
a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.|b Institute of Hepatology , Wenzhou Medical University , Wenzhou , China.
Fa-Ling
FL
Wu
c Department of Endocrinology , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
Wen-Yue
WY
Liu
d Department of Anesthesiology, Intensive Care, Emergency Medicine and Pain Therapy , Ziekenhuis Oost-Limburg , Genk , Belgium.
Sven
S
Van Poucke
e Global Medicines Development , AstraZeneca R&D , Alderley Park , UK.
Martin
M
Braddock
f Department of Infection Diseases , People Hospital of Wencheng County , Wenzhou , China.
Wei-Min
WM
Jin
g Institute of Biology Science , Wenzhou University , Wenzhou , China.|h School of Pharmacy , Wenzhou Medical University , Wenzhou , China.
Jian
J
Xiao
g Institute of Biology Science , Wenzhou University , Wenzhou , China.|h School of Pharmacy , Wenzhou Medical University , Wenzhou , China.
Xiao-Kun
XK
Li
a Department of Hepatology, Liver Research Center , the First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.|b Institute of Hepatology , Wenzhou Medical University , Wenzhou , China.
Ming-Hua
MH
Zheng
D000818:Animals; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D015398:Signal Transduction / Q000187:drug effects; D056811:Unfolded Protein Response / Q000187:drug effects*
Endoplasmic reticulum stress; acute-on-chronic liver failure; alcoholic liver disease; drug-induced liver injury; hepatocellular carcinoma; nonalcoholic fatty liver disease; therapeutic target