ER Stress-Mediated Cell Damage Contributes to the Release of EDA+ Fibronectin from Hepatocytes in Nonalcoholic Fatty Liver Disease
10.1007/s11596-017-1718-8
- Author:
HE LEI
1
;
YUAN FA-HU
;
CHEN TING
;
HUANG QIANG
;
WANG YU
;
LIU ZHI-GUO
Author Information
1. Department of Blood Transfusion
- Keywords:
fibronectin;
ER stress;
nonalcoholic fatty liver disease;
necrosis
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2017;37(2):217-225
- CountryChina
- Language:Chinese
-
Abstract:
Fibronectin containing extra domain A (EDA+ FN),a functional glycoprotein participating in several cellular processes,correlates with chronic liver disease.Herein,we aim to investigate the expression and secretion of EDA+ FN from hepatocytes in nonalcoholic fatty liver disease (NAFLD) and the underlying mechanisms.Circulating levels of EDA+ FN were determined by ELISA in clinical samples.Western blotting and flow cytometry were performed on L02 and HepG2 cell lines to analyze whether the levels of EDA+ FN were associated with endoplasmic reticulum (ER) stress-related cell death.Circulating levels of EDA+ FN in NAFLD patients were significantly higher than those in control subjects,and positively related with severity of ultrasonographic steatosis score.In cultured hepatocytes,palmitate up-regulated the expression of EDA+ FN in a dose-dependent manner.Conversely,when the cells were pretreated with 4-phenylbutyrate,a specific inhibitor of ER stress,up-regulation of EDA+ FN could be abrogated.Moreover,silencing CHOP by shRNA enhanced the release of EDA+ FN from hepatocytes following palmitate treatment,which was involved in ER stress-related cell damage.These findings suggest that the up-regulated level of EDA+ FN is associated with liver damage in NAFLD,and ER stress-mediated cell damage contributes to the release of EDA+ FN from hepatocytes.
