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微小RNA在损伤与修复中的作用

MicroRNAs in injury and repair.

作者信息

Gerlach Cory V, Vaidya Vishal S

机构信息

Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA.

Department of Medicine, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

出版信息

Arch Toxicol. 2017 Aug;91(8):2781-2797. doi: 10.1007/s00204-017-1974-1. Epub 2017 May 13.

Abstract

Organ damage and resulting pathologies often involve multiple deregulated pathways. MicroRNAs (miRNAs) are short, non-coding RNAs that regulate a multitude of genes at the post-transcriptional level. Since their discovery over two decades ago, miRNAs have been established as key players in the molecular mechanisms of mammalian biology including the maintenance of normal homeostasis and the regulation of disease pathogenesis. In recent years, there has been substantial progress in innovative techniques to measure miRNAs along with advances in targeted delivery of agents modulating their expression. This has expanded the scope of miRNAs from being important mediators of cell signaling to becoming viable quantitative biomarkers and therapeutic targets. Currently, miRNA therapeutics are in clinical trials for multiple disease areas and vast numbers of patents have been filed for miRNAs involved in various pathological states. In this review, we summarize miRNAs involved in organ injury and repair, specifically with regard to organs that are the most susceptible to injury: the liver, heart and kidney. In addition, we review the current state of knowledge on miRNA biology, miRNA biomarkers and nucleotide-based therapeutics designed to target miRNAs to prevent organ injury and promote repair.

摘要

器官损伤及由此引发的病变通常涉及多种失调的信号通路。微小RNA(miRNA)是一类短链非编码RNA,可在转录后水平调控众多基因。自二十多年前被发现以来,miRNA已被确立为哺乳动物生物学分子机制中的关键角色,包括维持正常的体内平衡以及调节疾病发病机制。近年来,在测量miRNA的创新技术以及调节其表达的药物靶向递送方面取得了重大进展。这已将miRNA的范畴从细胞信号传导的重要介质扩展至可行的定量生物标志物和治疗靶点。目前,miRNA疗法正在多个疾病领域进行临床试验,并且已针对涉及各种病理状态的miRNA提交了大量专利。在本综述中,我们总结了参与器官损伤和修复的miRNA,特别是针对那些最易受损伤的器官:肝脏、心脏和肾脏。此外,我们还综述了有关miRNA生物学、miRNA生物标志物以及旨在靶向miRNA以预防器官损伤和促进修复的基于核苷酸的疗法的当前知识状态。

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