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非编码 RNA 在急性肾损伤中的作用。

Noncoding RNAs in acute kidney injury.

机构信息

Department of Anesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany.

Cardiovascular Research Unit, Department of Population Health, Luxembourg Institute of Health, Luxembourg, Luxembourg.

出版信息

Kidney Int. 2018 Nov;94(5):870-881. doi: 10.1016/j.kint.2018.06.033.

Abstract

Acute kidney injury (AKI) is an important health issue concerning ∼50% of patients treated in intensive care units. AKI mainly occurs after sepsis, acute ischemia, nephrotoxicity, or hypoxia and leads to severe damage of the kidney and to an increased risk of mortality. The diagnosis of AKI is currently based on creatinine urea levels and diuresis. Yet, novel markers may improve the accuracy of this diagnosis at an early stage of the disease, thereby allowing early prevention and therapy, ultimately leading to a reduction in the need for renal replacement therapy and decreased mortality. Non-protein-coding RNAs or noncoding RNAs are central players in development and disease. They are important regulatory molecules that allow a fine-tuning of gene expression and protein synthesis. This regulation is necessary to maintain homeostasis, and its dysregulation is often associated with disease development. Noncoding RNAs are present in the kidney and in body fluids and their expression is modulated during AKI. This review article assembles the current knowledge of the role of noncoding RNAs, including microRNAs, long noncoding RNAs and circular RNAs, in the pathogenesis of AKI. Their potential as biomarkers and therapeutic targets as well as the challenges to translate research findings to clinical application are discussed. Although microRNAs have entered clinical testing, preclinical and clinical trials are needed before long noncoding RNAs and circular RNAs may be considered as useful biomarkers or therapeutic targets of AKI.

摘要

急性肾损伤(AKI)是一个重要的健康问题,约 50%的重症监护病房患者受到影响。AKI 主要发生在脓毒症、急性缺血、肾毒性或缺氧之后,会导致严重的肾脏损伤,并增加死亡率。AKI 的诊断目前基于肌酐、尿素水平和尿量。然而,新型标志物可能会提高疾病早期诊断的准确性,从而实现早期预防和治疗,最终减少对肾脏替代治疗的需求,降低死亡率。非编码 RNA 或非编码 RNA 是发育和疾病的核心参与者。它们是重要的调节分子,允许对基因表达和蛋白质合成进行微调。这种调节对于维持体内平衡是必要的,其失调通常与疾病的发展有关。非编码 RNA 存在于肾脏和体液中,其表达在 AKI 期间被调节。这篇综述文章汇集了非编码 RNA(包括 microRNA、长非编码 RNA 和环状 RNA)在 AKI 发病机制中的作用的最新知识。讨论了它们作为生物标志物和治疗靶点的潜力,以及将研究结果转化为临床应用所面临的挑战。虽然 microRNA 已经进入临床测试,但在长非编码 RNA 和环状 RNA 可能被认为是 AKI 的有用生物标志物或治疗靶点之前,还需要进行临床前和临床试验。

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