Chronic ethanol feeding enhances miR-21 induction during liver regeneration while inhibiting proliferation in rats
Chronic ethanol feeding enhances miR-21 induction during liver regeneration while inhibiting proliferation in rats
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DOI：
10.1152/ajpgi.00019.2012
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发表时间：
2012-09-01
影响因子：
4.5
通讯作者：
Hoek, Jan B.
中科院分区：
文献类型：
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作者：
Dippold, Rachael P.;Vadigepalli, Rajanikanth;Hoek, Jan B.
Dippold RP，Vadigepalli R，Gonye GE，Hoek JB.慢性乙醇喂养增强大鼠肝再生过程中miR-21的诱导，同时抑制增殖。美国生理学杂志胃肠和肝脏生理学303：G733-G743，2012年。首次发表于2012年7月12日; doi：10.1152/ajpgi.00019.2012. -肝再生是肝损伤后重要的修复反应。慢性乙醇消耗抑制和延迟实验动物的肝再生。我们研究了慢性乙醇处理对三分之二部分肝切除术（PHx）后前24小时内信使RNA（mRNA）和微小RNA（miRNA）表达谱的影响，发现乙醇喂养和成对喂养的肝脏miR-21表达均增加PHx后的对照大鼠。我们证明，在乙醇喂养的大鼠中，肝脏再生过程中miR-21表达的增加更为稳健。在乙醇喂养的大鼠和对照大鼠中，峰值miR-21表达均出现在PHx后24 h，对应于对照大鼠肝细胞S期的峰值，但在乙醇暴露的肝脏中没有，其中细胞周期延迟。对照大鼠PHx后24 h miR-21的诱导并不大于假手术引起的miR-21表达的增加。然而，在乙醇喂养的大鼠中，PHx比假手术更大程度地诱导miR-21。为了阐明肝脏再生过程中miR-21表达增加的意义，我们使用我们小组编制的基因表达数据进行了无偏的全局靶标分析。我们的分析表明，miR-21可能发挥更大的作用，在乙醇喂养大鼠再生过程中的基因表达的调控比对照组大鼠。我们对miR-21潜在靶点的分析表明，miR-21影响广泛的靶过程，并可能在乙醇处理动物的肝再生抑制条件下具有广泛的调节作用。
Dippold RP, Vadigepalli R, Gonye GE, Hoek JB. Chronic ethanol feeding enhances miR-21 induction during liver regeneration while inhibiting proliferation in rats. Am J Physiol Gastrointest Liver Physiol 303: G733-G743, 2012. First published July 12, 2012; doi:10.1152/ajpgi.00019.2012.-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.