MicroRNAs: master regulators of ethanol abuse and toxicity?
MicroRNAs: master regulators of ethanol abuse and toxicity?
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DOI：
10.1111/j.1530-0277.2009.01126.x
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Hereld D
中科院分区：
文献类型：
--
作者：
Miranda RC;Pietrzykowski AZ;Tang Y;Sathyan P;Mayfield D;Keshavarzian A;Sampson W;Hereld D
乙醇对人体的生理和健康有着复杂的影响。乙醇不仅是一种成瘾性物质，而且还是一种胎儿致畸剂、一种成人神经毒素、一种肝脏和心血管疾病、炎症、骨丢失和骨折易感性的病原体。大量的基因和信号机制与乙醇的有害作用有关，这导致了乙醇是一种“肮脏的药物”的建议。一个重要的问题是，是否有细胞的“主开关”可以解释乙醇的这些多效性效应？microRNAs（miRNAs）是近年来发现的细胞转录组和蛋白质组的主要调控因子。miRNA在健康和疾病中塑造组织和器官的分化和功能方面发挥着越来越重要的作用。这篇评论讨论了新的证据，表明乙醇敏感的miRNAs确实是调节主开关。更具体地说，miRNAs控制耐受性的发展，这是乙醇成瘾的关键组成部分。其他滥用药物也靶向一些乙醇敏感的miRNAs，这表明成瘾的共同生化机制。这篇综述还讨论了miRNA介导几种乙醇病理学的证据，包括暴露胎儿神经干细胞增殖和分化的破坏，导致内毒素血症和酒精性肝病的肠道渗漏，以及可能的肝细胞癌和其他胃肠道癌症。最后，这篇综述提供了一个新的调查的潜在作用的miRNAs作为介质的乙醇对炎症和骨折愈合的影响，以及作为诊断生物标志物和作为酒精相关疾病的治疗干预措施的目标的潜力。
Ethanol exerts complex effects on human physiology and health. Ethanol is not only addictive, but it is also a fetal teratogen, an adult neurotoxin, and an etiologic agent in hepatic and cardiovascular disease, inflammation, bone loss and fracture susceptibility. A large number of genes and signaling mechanisms have been implicated in ethanol's deleterious effects, leading to the suggestion that ethanol is a “dirty drug”. An important question is, are there cellular “master-switches” that can explain these pleiotropic effects of ethanol? MicroRNAs (miRNAs) have been recently identified as master regulators of the cellular transcriptome and proteome. miRNAs play an increasingly appreciated and crucial role in shaping the differentiation and function of tissues and organs in both health and disease. This critical review discusses new evidence showing that ethanol-sensitive miRNAs are indeed regulatory master-switches. More specifically, miRNAs control the development of tolerance, a crucial component of ethanol addiction. Other drugs of abuse also target some ethanol-sensitive miRNAs suggesting that common biochemical mechanisms underlie addiction. This review also discusses evidence that miRNAs mediate several ethanol pathologies, including disruption of neural stem cell proliferation and differentiation in the exposed fetus, gut leakiness that contributes to endotoxemia and alcoholic liver disease, and possibly also hepatocellular carcinomas and other gastrointestinal cancers. Finally, this review provides a perspective on emerging investigations into potential roles of miRNAs as mediators of ethanol's effects on inflammation and fracture healing, as well as the potential for miRNAs as diagnostic biomarkers and as targets for therapeutic interventions for alcohol related disorders.
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影响因子：
12.3
作者：
Blow MJ;Grocock RJ;van Dongen S;Enright AJ;Dicks E;Futreal PA;Wooster R;Stratton MR
通讯作者：
Stratton MR
DOI：
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发表时间：
1999-08-17
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
3.4
作者：
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通讯作者：
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DOI：
10.1073/pnas.0810909106
发表时间：
2009-03-31
影响因子：
11.1
作者：
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通讯作者：
Locati, Massimo