Suppression of IRE1α Attenuated the Fatty Degeneration in Parenteral Nutrition-Related Liver Disease (PNALD) Cell Model.

Ningxun Cui,Mingling Cui,Jie Li,Xiaoli Zhu,Xueping Zhu

doi:10.1155/2020/7517540

Abstract

Aims To model the parenteral nutrition-associated liver disease (PNALD) in rat normal hepatocytes BRL and investigate the role of endoplasmic reticulum stress- (ERS-) related IRE1α signal in the process of PNALD. Methods The BRL cells were treated with different concentrations of soybean oil emulsion (SO) to induce hepatocyte fatty degeneration. The PNALD cell disease model was further confirmed by analysis of Oil Red O staining and biochemical parameters. Next, the IRE1α signal in the process of PNALD. α signal in the process of PNALD. α signal in the process of PNALD. α signal in the process of PNALD. Results The results of Oil Red O staining indicated that the PNALD was successfully established in BRL cells and the CCK-8 data indicated which 0.6% that SO was further applied to the experiment owing to its better induction of PNALD and less toxicity to the cells. Besides, the value of biochemical parameters (TBIL, DBIL, ALT, and AST) was also elevated in the SO group compared with the NG group. After knockdown of IRE1α signal in the process of PNALD. α signal in the process of PNALD. Conclusion IRE1α was induced in PNALD cell model and suppression of IRE1α resulted in reduced steatosis in this cell disease model. Taken together, our data suggested that the IRE1α pathway may be involved in the development of PNALD.α signal in the process of PNALD. α signal in the process of PNALD. α signal in the process of PNALD.

Highlights

Parenteral nutrition (PN) has revolutionized the lifestyle of the neonates with growth defect caused by intestinal dysfunction [1]
The IRE1α-suppressed BRL cell line was established to investigate its role in the development of PN-associated liver disease (PNALD)
The results demonstrated that when IRE1α is inhibited, the development of PNALD was decreased, suggesting that blocking of endoplasmic reticulum (ER) stress pathway could benefit for liver function when suffering PNALD

Summary

Introduction

Parenteral nutrition (PN) has revolutionized the lifestyle of the neonates with growth defect caused by intestinal dysfunction [1]. UPR was regulated by three transducers, inositol-requiring enzyme 1 (IRE1), protein kinase R-like ER kinase (PERK), and activating transcription factor 6 (ATF6), in the ER network [14]. They bind to Gastroenterology Research and Practice glucose-regulated protein 78 (GRP-78) on the ER membrane to promote protein folding and prevent protein aggregation using adenosine triphosphate (ATP). Our previous study demonstrated that soybean oil-based lipid emulsions could induce significant ER and mitochondrial damage, resulting in ER stress in primary rabbit hepatocytes [21, 22]. IRE1α was suppressed by specific shRNA in hepatocytes to investigate the role of ER stress in PNALD model

Materials and Methods

Results

Discussion

Conflicts of Interest