原发性未折叠蛋白反应传感器内质网-核信号1在人类非酒精性脂肪性肝炎患者的肝脏中下调

El Hussain Shamsa, Kezhong Zhang
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摘要

未折叠蛋白反应(UPR)是一种来自内质网(ER)的优雅信号通路,可保护细胞免受内质网内未折叠或错误折叠蛋白积累引起的应激。ER-to-Nucleus Signaling 1 (IRE1,也称为ERN1)是内质网定位的蛋白激酶和核糖核酸内切酶(RNase),是UPR信号通路中最保守的换能器。在这项研究中,我们研究了IRE1在人类非酒精性脂肪性肝炎(NASH)患者肝脏中的表达水平。方法:基于从公共领域获得的微阵列基因表达数据集,我们分析了人类NASH患者肝脏中初级UPR传感器IRE1的表达谱。结果:我们的分析表明,与非NASH肥胖患者相比,人类肥胖NASH患者肝脏中IRE1的表达水平降低。结论:我们的分析结果与ire1介导的UPR在维持细胞稳态和功能以及保护生物体免受损伤中的作用是一致的。本研究为人类NASH中UPR信号通路的激活和功能参与提供了重要信息。
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The primary unfolded protein response transducer endoplasmic reticulum-to-nucleus signaling 1 is downregulated in livers of human nonalcoholic steatohepatitis patients
Background: The Unfolded Protein Response (UPR) is an elegant signaling pathway from the Endoplasmic Reticulum (ER) to protect cells from stress caused by accumulation of unfolded or misfolded proteins in the ER lumen. ER-to-Nucleus Signaling 1 (IRE1, also called ERN1), an ER-localized protein kinase and endoribonuclease (RNase), is the most conserved transducer of the UPR signaling pathway. In this study, we investigated expression levels of IRE1 in the livers of human non-alcoholic steatohepatitis (NASH) patients. Methods: We analyzed the expression profiles of the primary UPR transducer IRE1 in the livers of human NASH patients based on the microarray gene expression datasets obtained from public domain. Results: Our analyses indicated that expression levels of IRE1 were decreased in the livers of human obese patients with NASH, compared to those of obese patients without NASH. Conclusions: Our analysis result is consistent with the role of IRE1-mediated UPR in preserving cellular homeostasis and functions and in protecting organisms from injuries. This study provides important information in regard to the activation and functional involvement of the UPR signaling pathway in human NASH.
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