Abstract

This study aimed to investigate the mechanism of mangiferin on regulating endoplasmic reticulum (ER) stress in acute liver injury. The mouse model of acute liver injury was established by injection of LPS/D-GalN. The primary mouse hepatocytes were stimulated with LPS to induce the in vitro model. The effect of miR-20a/101a on the luciferase activity of Nrf2 3′-UTR was assessed by luciferase reporter assay. Mangiferin improved the liver function, inhibited the oxidative stress and ER stress and down-regulated the expressions of miR-20a and miR-101a in LPS/D-GalN-induced mice and LPS-induced hepatocytes. The knockdown of miR-20a and miR-101a co-operatively alleviated ER stress of LPS-induced hepatocytes. miR-20a and miR-101a both targeted Nrf2 and the over-expression of miR-20a or miR-101a decreased Nrf2 protein level, while their silences increased Nrf2 protein level. The silence of miR-20a and miR-101a promoted Nrf2 expression and inhibited the ER stress in LPS-induced hepatocytes, while the knockdown of Nrf2 reversed these effects. The over-expression of miR-20a and miR-101a eliminated the effects of mangiferin on Nrf2 protein level and ER stress in LPS-induced hepatocytes and Nrf2 over-expression altered these trends. Our findings suggest that mangiferin alleviates ER stress in acute liver injury by regulating the miR-20a/miR-101a-Nrf2 axis.

中文翻译：

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芒果苷通过调节miR-20a / miR-101a-Nrf2轴减轻急性肝损伤中的内质网应激。

摘要

本研究旨在探讨芒果苷调节急性肝损伤中内质网（ER）应激的机制。通过注射LPS / D-GalN建立小鼠急性肝损伤模型。LPS刺激小鼠原代肝细胞体外诱导。模型。通过荧光素酶报告基因分析评估miR-20a / 101a对Nrf2 3'-UTR荧光素酶活性的影响。芒果苷改善了LPS / D-GalN诱导的小鼠和LPS诱导的肝细胞的肝功能，抑制了氧化应激和ER应激，并下调了miR-20a和miR-101a的表达。miR-20a和miR-101a的组合可协同减轻LPS诱导的肝细胞的内质网应激。miR-20a和miR-101a都靶向Nrf2，miR-20a或miR-101a的过表达降低Nrf2蛋白水平，而沉默则增加Nrf2蛋白水平。miR-20a和miR-101a的沉默可促进Lr诱导的肝细胞中Nrf2的表达并抑制ER应激，而敲低Nrf2可逆转这些作用。miR-20a和miR-101a的过表达消除了芒果苷对LPS诱导的肝细胞中Nrf2蛋白水平和内质网应激的影响，而Nrf2的过表达改变了这些趋势。我们的发现表明，芒果苷通过调节miR-20a / miR-101a-Nrf2轴减轻了急性肝损伤中的内质网应激。