Study Of The Effect And Mechanism Of Protein Disulfide Isomerase A3Precursor In Nonalcoholic Fatty Liver Disease

AIM:Nonalcoholic fatty liver disease (NAFLD) has emerged as one of the most common chronic liver disease over the past decades. Recent studies have shown that endoplasmic reticulum stress (ERS) plays a pivotal role during the development of NAFLD. This study aims to analyze the potential role of one of the ER chaperones protein disulfide isomerase A3precursor (PDIA3) in NAFLD.METHOD:Palmitic acid (PA) was used to set up cell models of NAFLD in Human liver L02cell line. On this basis, we used molecular biology methods such as small molecular RNA interference (siRNA), Western Blot, cell apoptosis detection to explore the potential role of PDIA3during the development of NAFLD.RESULTS:(1) NAFLD cell models were established successfully by PA;(2) The expression level of PDIA3was increased in the cell models of NAFLD;(3) siRNA-mediated knockdown of PDIA3in L02cells not only increased the cellular lipid accumulation, but also exacerbated hepatocytes apoptosis induced by PA;(4) The knockdown of PDIA3up-regulated the protein expression of the fatty acid synthase (FAS), phospho-PKR-like ER kinase (P-PERK), glucose-regulated protein78(GRP78) and C/EBP homologous protein (CHOP).CONCLUSIONS:(1) PDIA3was associated with the pathogenesis of NAFLD;(2) siRNA-mediated knockdown of PDIA3in L02cells increased the cellular lipid accumulation induced by PA, and the potential mechanism may be associated with the up-regulation of FAS expression, which inducing endogenous fatty acid synthesis;(3) siRNA-mediated knockdown of PDIA3in L02cells exacerbated hepatocytes ERS and apoptosis induced by PA, and the potential mechanism may be associated with the activation of PERK-CHOP pathway. Our results may help clarify the pathogenesis of NAFLD and point to potential target for diagnostic and therapeutic intervention.