Hepatocellular iNOS protects liver from NASH through Nrf2-dependent activation of HO-1.
Hepatocellular iNOS protects liver from NASH through Nrf2-dependent activation of HO-1.
复制标题
肝细胞 iNOS 通过 Nrf2 依赖性激活 HO-1 来保护肝脏免受 NASH 的影响。
DOI：
10.1016/j.bbrc.2019.04.144
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发表时间：
2019-06
期刊：
影响因子：
--
通讯作者：
Sun Jie
中科院分区：
文献类型：
--
作者：
Qiao Yingli;Li Xuehua;Zhang Xueli;Xiao Fei;Zhu Yu;Fang Zheping;Sun Jie
非酒精性脂肪性肝炎（NASH）涉及多种分子事件。诱导型一氧化氮合酶（iNOS）在NASH进展中的作用尚未达成共识。因此，本研究使用骨髓移植的iNOS嵌合体小鼠在高脂饮食（HFD）条件下研究iNOS在NASH发病机制中的作用。嵌合小鼠喂食HFD 16周，并用油酸（OA）刺激原代肝细胞。研究了iNOS在NASH中作用的分子机制。在HFD小鼠和OA刺激的肝细胞中观察到的显著的肝脂肪变性和损伤被肝细胞衍生的iNOS减少。从机制上讲，iNOS通过增加核因子红细胞2相关因子2（Nrf-2）与HO-1基因启动子的结合来上调血红素加氧酶1（HO-1）。总之，肝细胞来源的iNOS可能通过上调HO-1通过Nrf-2对NASH的进展发挥保护作用。肝细胞iNOS的上调可能代表对抗NASH的潜在新治疗范例。
Multiple molecular events are involved in non-alcoholic steatohepatitis (NASH). There is no consensus on the role of inducible nitric oxide synthase (iNOS) in the progression of NASH. The present study therefore investigated the role of iNOS in NASH pathogenesis using bone marrow-transplanted iNOS chimeric mice under high-fat diet (HFD) conditions. The chimeric mice were fed a HFD for 16 wk, and primary hepatocytes were stimulated with oleic acid (OA). The molecular mechanisms underlying the role of iNOS in NASH were investigated. Marked hepatic steatosis and injury observed in the HFD mice and OA-stimulated hepatocytes were reduced by hepatocyte-derived iNOS. Mechanistically, iNOS upregulated heme oxygenase 1 (HO-1) by augmenting nuclear factor erythroid 2-related factor 2 (Nrf-2) binding to the HO-1 gene promoter. In conclusion, hepatocyte-derived iNOS may play a protective role against the progression of NASH by upregulating HO-1 through Nrf-2. Upregulation of hepatocellular iNOS may represent a potentially new therapeutic paradigm to combat NASH.
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影响因子：
25.7
作者：
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影响因子：
12.4
作者：
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通讯作者：
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影响因子：
25.7
作者：
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影响因子：
13.5
作者：
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