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首页> 外文期刊>American Journal of Physiology >Chronic ethanol feeding enhances miR-21 induction during liver regeneration while inhibiting proliferation in rats
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Chronic ethanol feeding enhances miR-21 induction during liver regeneration while inhibiting proliferation in rats

机译：长期补充乙醇可增强肝脏再生期间的miR-21诱导，同时抑制大鼠的增殖

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Liver regeneration is an important repair response to liver injury. Chronic ethanol consumption inhibits and delays liver regeneration in experimental animals. We studied the effects of chronic ethanol treatment on messenger RNA (mRNA) and microRNA (miRNA) expression profiles during the first 24 h after two-thirds partial hepatectomy (PHx) and found an increase in hepatic miR-21 expression in both ethanol-fed and pair-fed control rats after PHx. We demonstrate that the increase of miR-21 expression during liver regeneration is more robust in ethanol-fed rats. Peak miR-21 expression occurs at 24 h after PHx in both ethanol-fed and control rats, corresponding to the peak of hepatocyte S phase in control rats, but not in ethanol-exposed livers in which cell cycle is delayed. The induction of miR-21 24 h after PHx in control rats is not greater than the increase in expression of miR-21 due to sham surgery. However, in the ethanol-fed rat, miR-21 is induced to a greater extent by PHx than by sham surgery. To elucidate the implications of increased miR-21 expression during liver regeneration, we employed unbiased global target analysis using gene expression data compiled by our group. Our analyses suggest that miR-21 may play a greater role in regulating gene expression during regeneration in the ethanol-fed rat than in the control rat. Our analysis of potential targets of miR-21 suggests that miR-21 affects a broad range of target processes and may have a widespread regulatory role under conditions of suppressed liver regeneration in ethanol-treated animals.
机译：肝再生是对肝损伤的重要修复反应。慢性乙醇的消耗抑制并延迟了实验动物的肝脏再生。我们研究了三分之二部分肝切除术（PHx）后头24小时内，慢性乙醇处理对信使RNA（mRNA）和微小RNA（miRNA）表达谱的影响，并发现在两种乙醇喂养下，肝脏miR-21表达均增加和PHx后配对喂养的对照大鼠。我们证明，在乙醇喂养的大鼠中，肝再生期间miR-21表达的增加更为牢固。 miR-21的峰值表达出现在PHx后24小时，由乙醇喂养的大鼠和对照组的大鼠均出现，这与对照组大鼠的肝细胞S期的峰值相对应，但在乙醇暴露的肝脏（其细胞周期被延迟）中则不存在。对照大鼠在PHx后24小时对miR-21的诱导作用不大于假手术引起的miR-21表达的增加。然而，在用乙醇喂养的大鼠中，与假手术相比，PHx可以更大程度地诱导miR-21。为了阐明在肝再生过程中增加miR-21表达的影响，我们使用了由我们小组收集的基因表达数据进行的无偏全局靶点分析。我们的分析表明，与对照大鼠相比，在以乙醇喂养的大鼠中再生期间，miR-21可能在调节基因表达中发挥更大的作用。我们对miR-21潜在靶标的分析表明，miR-21影响广泛的靶标过程，并且在乙醇处理动物的肝脏再生受到抑制的条件下可能具有广泛的调节作用。

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