ROS/NF-κB Signaling Pathway-Mediated Transcriptional Activation of TRIM37 Promotes HBV-Associated Hepatic Fibrosis,Molecular Therapy - Nucleic Acids

当前位置： X-MOL 学术 › Mol. Ther. Nucl. Acids › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

ROS/NF-κB Signaling Pathway-Mediated Transcriptional Activation of TRIM37 Promotes HBV-Associated Hepatic Fibrosis
Molecular Therapy - Nucleic Acids ( IF 6.5 ) Pub Date : 2020-08-19 , DOI: 10.1016/j.omtn.2020.08.014
Haina Xie ₁ , Dongyu Xie ₂ , Jingxian Zhang ₃ , Wenye Jin ₃ , Yue Li ₃ , Jun Yao ₃ , Zhiqiang Pan ₁ , Donghao Xie ₄

Affiliation

Hepatic fibrosis is an inflammatory response that leads to liver cirrhosis in the most advanced condition. Liver cirrhosis is a leading cause of deaths associated with liver diseases; hence, understanding the underlying mechanisms of hepatic fibrosis is critical to develop effective therapies. Tripartite motif (TRIM) family proteins have been shown to be involved in liver fibrosis; however, the exact role of several TRIM proteins in this process remained unexplored. In this study, we investigated the role of TRIM37 in hepatitis B virus (HBV)-associated hepatic fibrosis. We analyzed TRIM37 expression in hepatic fibrosis patients and performed functional and mechanistic studies in tissue culture and mouse models to identify the role of TRIM37 in hepatic fibrosis. We found an increased expression of TRIM37 in hepatic fibrosis patients. Mechanistically, we showed that TRIM37 physically interacts with SMAD7 and promotes ubiquitination-mediated degradation of SMAD7, and that SMAD7 is a key mediator of TRM37-induced hepatic fibrosis. Furthermore, we showed nuclear factor κB (NF-κB) activation mediated by reactive oxygen species (ROS) is necessary for the transcriptional induction of TRIM37 during HBV infection. Our study shows TRIM37 as an important promoter of HBV-associated hepatic fibrosis.

中文翻译：

ROS/NF-κB 信号通路介导的 TRIM37 转录激活促进 HBV 相关肝纤维化

肝纤维化是一种炎症反应，在最晚期导致肝硬化。肝硬化是肝病相关死亡的主要原因;因此，了解肝纤维化的潜在机制对于开发有效的疗法至关重要。三联基序（TRIM）家族蛋白已被证明与肝纤维化有关;然而，几种 TRIM 蛋白在此过程中的确切作用仍未得到探索。在这项研究中，我们调查了 TRIM37 在乙型肝炎病毒（HBV）相关肝纤维化中的作用。我们分析了肝纤维化患者 TRIM37 的表达，并在组织培养和小鼠模型中进行了功能和机制研究，以确定 TRIM37 在肝纤维化中的作用。我们发现肝纤维化患者中 TRIM37 的表达增加。从机制上讲，我们表明 TRIM37 与 SMAD7 发生物理相互作用并促进泛素化介导的 SMAD7 降解，并且 SMAD7 是 TRM37 诱导的肝纤维化的关键介质。此外，我们发现活性氧（ROS）介导的核因子 κB （NF-κB）激活对于 HBV 感染期间 TRIM37 的转录诱导是必需的。我们的研究表明 TRIM37 是 HBV 相关肝纤维化的重要启动子。

更新日期：2020-08-19

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文