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Hepatology：低氧诱导因子2通过上调富组织蛋白水平来促进非酒精性脂肪肝的进展

2018-06-26 MedSci MedSci原创

低氧诱导因子2富组织蛋白非酒精性脂肪肝
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这些结果表明，肝细胞内的HIF-2alpha激活是NAFLD的一个关键特征，并通过上调HRGP水平，促进疾病发展。

研究背景：非酒精性脂肪肝(NAFLD)的发展机制尚不完全清楚。低氧和低氧诱导因子(HIFs)与慢性肝病的发病机制有关，但在NAFLD的演变过程中，HIF-2alpha在其中发挥的作用，还未被探究过。

研究方法和结果：研究表明，HIF-2alpha在一组肝纤维化处于不同分期的NAFLD患者的肝细胞胞质和胞核中过表达。同样的特征也出现在以蛋氨酸/胆碱缺乏饮食诱导的脂肪性肝炎小鼠身上。无论是以胆碱缺乏的l -氨基酸还是蛋氨酸/胆碱缺乏诱导的脂肪肝模型中，肝细胞缺失HIF-2alpha基因的小鼠通过减低肝实质损伤、脂肪肝、小叶炎症和肝纤维化的发展来改善NAFLD的进化。HIF-2alpha基因缺失小鼠的NAFLD疾病进展的改善，与最近提出的维持巨噬细胞M1极化的富组织蛋白(HRGP)生成下调有关。体外实验证实，肝细胞HRGP表达的提高是依赖于低氧和HIF-2alpha的。最后，对NAFLD患者的标本进行分析，发现所有肝细胞核染色HIF-2alpha阳性的患者，HRGP均过表达，且HIF-2alpha与HRGP肝脏转录水平呈显著正相关。

研究结论：这些结果表明，肝细胞内的HIF-2alpha激活是NAFLD的一个关键特征，并通过上调HRGP水平，促进疾病发展。

原始出处：

Morello E， Sutti S， Foglia B， et al. Hypoxia-inducible factor 2alpha drives nonalcoholic fatty liver progression by triggering hepatocyte release of histidine-rich glycoprotein. Hepatology， 2018， 67(6)， 2196-2214.

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    2018-08-21 yangshch

    #酒精性脂肪肝#

    0

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    2018-07-18 huiwelcome

    #酒精性#

    0

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    2018-12-03 Tommy1958

    #非酒精性#

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    2018-07-02 荒郊野树

    学习

    0

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    2018-06-29 荒郊野树

    学习

    0

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    2018-06-28 gwc384

    #EPA#

    0