Resveratrol prevents liver damage in MCD-induced steatohepatitis mice by promoting SIGIRR gene transcription
Resveratrol prevents liver damage in MCD-induced steatohepatitis mice by promoting SIGIRR gene transcription
复制标题
白藜芦醇通过促进 SIGIRR 基因转录来预防 MCD 诱导的脂肪性肝炎小鼠的肝损伤
DOI：
10.1016/j.jnutbio.2020.108400
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发表时间：
2020-08-01
影响因子：
5.6
通讯作者：
Shi, Ying
中科院分区：
文献类型：
--
作者：
Che, YuanYuan;Shi, Xu;Shi, Ying
持续炎症是非酒精性脂肪性肝病发展为肝硬化和肝癌的主要原因之一，降低炎症因子的表达可能是缓解非酒精性脂肪性肝炎（NASH）发展的有效策略。SIGIRR是白细胞介素-1受体家族的一员，已被证明可以抑制炎症细胞因子的产生，其下调或缺失被认为是器官炎症损伤的重要原因。在本研究中，我们发现白藜芦醇有效地诱导了SIGIRR启动子的转录活性，并增加了人肝细胞和小鼠肝脏中SIGIRR mRNA的水平。此外，研究了白藜芦醇对蛋氨酸/胆碱缺乏饮食诱导的NASH小鼠模型的潜在影响。白藜芦醇可维持小鼠肝脏SIGIRR的表达水平。白藜芦醇干预可缓解NASH进展；降低丙氨酸转氨酶和天冬氨酸转氨酶水平；下调肿瘤坏死因子- α、白细胞介素(IL)-6、IL-1 β和转化生长因子- β mRNA和蛋白水平。此外，SIGIRR的增加可能会在体内和体外阻断toll样受体/核因子- κ B信号通路的活性。在体外实验中，白藜芦醇预处理对泡沫巨噬细胞释放的炎症细胞因子引起的肝细胞损伤有保护作用，这些细胞因子参与NASH的发展。然而，白藜芦醇在炎症细胞因子微环境中不能有效诱导肝细胞SIGIRR基因转录。综上所述，白藜芦醇是实用的，可以作为SIGIRR蛋白的激动剂负向调节肝脏炎症因子的表达，提示适当摄入白藜芦醇可能是预防NASH发生发展的潜在途径。(C) 2020爱思唯尔公司版权所有。
Persistent inflammation is one of the main reasons that nonalcoholic fatty liver disease develops into cirrhosis and liver cancer, and reducing the expression of inflammatory factors may be an effective strategy to alleviate the development of nonalcoholic steatohepatitis (NASH). SIGIRR, a member of the interleukin-1 receptor family, has been shown to inhibit the production of inflammatory cytokines, and its down-regulation or deletion has been suggested to be an important cause of inflammatory damage to organs. In this study, we identified that resveratrol efficiently induced the transcriptional activity of the SIGIRR promoter and also increased SIGIRR mRNA levels in human hepatocytes and mouse livers. Furthermore, the potential effects of resveratrol on a methionine/choline-deficient diet-induced NASH mouse model were investigated. Resveratrol maintained the expression level of SIGIRR in the mouse liver. Resveratrol intervention alleviated NASH progression; decreased the levels of alanine aminotransferase and aspartate aminotransferase; and down-regulated tumor necrosis factor-alpha, interleukin (IL)-6, IL-1 beta and transforming growth factor-beta mRNA and protein levels. Additionally, increased SIGIRR potentially blocked the activity of the Toll-like receptor/nuclear factor-kappa B signaling pathway both in vivo and in vitro. In vitro, resveratrol pretreatment protected against hepatocyte injury caused by foamy macrophage-released inflammatory cytokines, which are involved in the development of NASH. However, resveratrol did not effectively induce hepatocyte SIGIRR gene transcription in the inflammatory cytokine microenvironment. In conclusion, resveratrol is practical and acts as an agonist of the SIGIRR protein to negatively regulate the expression of inflammatory factors in liver, suggesting that appropriate intake may be a potential way to prevent the occurrence and development of NASH. (C) 2020 Elsevier Inc. All rights reserved.