FAM172A Deletion May Enhance Hepatic Steatosis by Promoting ER Stress
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ORIGINAL ARTICLE
FAM172A Deletion May Enhance Hepatic Steatosis by Promoting ER Stress Fan Xiao1 · Meixin Gao2 · Junru Yang2 · Lingling He2 · Hongshan Wei2 Received: 10 October 2019 / Accepted: 1 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Background Endoplasmic reticulum (ER) stress is one of the major causes to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Our previous study showed that maintains the homeostasis of ER could effectively alleviate NAFLD. In this study, we found that the loss of FAM172A increased ER stress. Aims The aims of this study were to explore whether FAM172A could improve NAFLD by inhibiting ER stress. Methods The expression levels of FAM172A and ER stress were detected by western blot. The method of immunofluorescence was used to determine FAM172A location. The interacted proteins of FAM172A were identified by immunocoprecipitation. The methods of MTS and caspase-3/7 activity were taken to confirm the effect of FAM172A on cell viability and proliferation. The expression levels of inflammation were detected by qPCR. Results We confirmed that FAM172A might alleviate NAFLD through inhibiting ER stress. Loss of FAM172A increased the expressions of ATF6, peIF2α, but decreased the expression of IRE1α. Then, it was shown that FAM172A located in ER and FAM172A directly interacted with ATF6 and peIF2α and IRE1α. More importantly, the binding of FAM172A and eIF2a in tunicamycin-treated group increased significantly compared with the control group. However, the binding of FAM172A and ATF6 or IRE1α did not change. Next, we found that the lack of FAM172A could produce more apoptosis and inflammation. Conclusions Our results suggest that FAM172A improve steatosis by alleviating ER stress. Keywords FAM172A · Endoplasmic reticulum stress · Steatosis · Nonalcoholic fatty liver disease
Introduction The endoplasmic reticulum (ER), one of the largest cellular organelles, is responsible for the proper assembly and posttranslational modification of proteins destined for intracellular organelles and the cell surface. ER stress can initiate unfolded protein response (UPR). UPR signaling includes three pathways, namely, protein kinase RNA-like endoplasmic reticulum kinase inositol-requiring enzyme 1 Fan Xiao, Meixin Gao, Junru Yang and Lingling He have contributed equally to this work. * Hongshan Wei [email protected] 1
Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
Department of Gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
2
(IRE1)-spliced X box binding protein 1 (sXBP1), (PERK)eukaryotic translation initiation factor 2-activating transcription factor 4 (ATF4) and ATF6. The ER stress sensors together initiate protective UPR to increase molecular chaperone levels, attenuate protein synthesis, and ER protein loading and up-regulate ER-associated protein degradation and ER
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