The Role of eIF2α in the Collagen Production in Hepatic Stellate Cell is Associated with Autophagic and Apoptotic Signaling

Abstract

Background & AimsStudies have documented cellular apoptosis, autophagy and endoplasmic reticulum (ER) stress participate in the liver fibrogenesis. However, the specific mechanism remains unclear. This study was aimed to determine whether and how eIF2α protein play a role in the collagen generation in hepatic stellate cell (HSC) via autophagic signaling events.MethodsHSC‐LX2 cell line was activated by transforming growth factor beta1 (TGF‐β1) in the presence of eIF2α plasmid or vehicle control. Real‐time fluorescence quantitative PCR was then performed to compare the differential mRNA level of COL1, eIF2α, CHOP, Bcl‐2 and Bax. Western Blot was performed to analyze the protein expression of α‐SMA, COL1, LC3, P62, eIF2α, P‐eIF2α and Bcl‐2 in LX2 cells. Meanwhile, the numbers of apoptotic cells were measured by flow cytometry.ResultsCompare to vehicle control, the ER stress hallmarks of eIF2α, CHOP were at lower level in HSC‐LX2 cells in TGF‐β1 treated condition. While transfected eIF2α plasmid in HSC‐LX2 cells, it was found that CHOP and BAX significantly increased in these cells but substantial reduction in LC3, P62, Bcl‐2, α‐SMA and COL1 v.s. control(<0.05). Moreover, thus exogenously enhancing of eIF2α gene was found to induce apoptosis of HSC‐LX2 cells with a 50% increment (<0.05).ConclusionsOverexpression of eIF2α in HSCs may trigger autophagy inhibition and apoptosis promotion, thereby reduce collagen production in these cells, which provide a potential therapeutic strategy for hepatic fibrosis.Support or Funding InformationSupported by NSFC Grants 81360077, 81860654, 30630145, 81172260 and GXNSFC Grants 2015GXNSFDA139022 to Guo ZhangThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.