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综述:微小 RNA 在肾脏疾病中的作用。

Review: The role of microRNAs in kidney disease.

机构信息

Departments of Renal Medicine, Flinders Medical Centre, Flinders University, Adelaide, South Australia, Australia.

出版信息

Nephrology (Carlton). 2010 Sep;15(6):599-608. doi: 10.1111/j.1440-1797.2010.01363.x.

Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that modulate physiological and pathological processes by inhibiting target gene expression via blockade of protein translation or by inducing mRNA degradation. These miRNAs potentially regulate the expression of thousands of proteins. As a result, miRNAs have emerged rapidly as a major new area of biomedical research with relevance to kidney disease. MiRNA expression has been shown to differ between the kidney and other organs as well as between different kidney regions. Furthermore, miRNAs have been found to be functionally important in models of podocyte development, diabetic nephropathy and polycystic kidney disease. Of particular interest, podocyte-specific deletion of Dicer, a key enzyme in the biogenesis of miRNA, results in proteinuria and severe renal impairment in mice. One miRNA (miR-192) can also act as an effector of transforming growth factor-β activity in the high-glucose environment of diabetic nephropathy. Differential expression of miRNAs has been reported in kidney allograft rejection. It is anticipated that future studies involving miRNAs will generate new insights into the complex pathophysiology underlying various kidney diseases, generate diagnostic biomarkers and might be of value as therapeutic targets for progressive kidney diseases. The purpose of this review is to highlight key miRNA developments in kidney diseases and how this might influence the diagnosis and management of patients with kidney disease in the future.

摘要

微小 RNA(miRNA)是短的非编码 RNA,通过阻断蛋白质翻译或诱导 mRNA 降解来抑制靶基因表达,从而调节生理和病理过程。这些 miRNA 可能调节数千种蛋白质的表达。因此,miRNA 迅速成为与肾脏疾病相关的生物医学研究的一个主要新领域。已经表明,miRNA 的表达在肾脏和其他器官之间以及肾脏的不同区域之间存在差异。此外,已经发现 miRNA 在足细胞发育、糖尿病肾病和多囊肾病的模型中具有功能重要性。特别有趣的是,miRNA 生物发生的关键酶 Dicer 在足细胞中的特异性缺失导致小鼠蛋白尿和严重的肾功能损害。一种 miRNA(miR-192)也可以作为转化生长因子-β在糖尿病肾病高葡萄糖环境中的效应物。在肾移植排斥反应中已经报道了 miRNA 的差异表达。预计未来涉及 miRNA 的研究将为各种肾脏疾病的复杂病理生理学提供新的见解,产生诊断生物标志物,并可能作为进行性肾脏疾病的治疗靶点具有价值。本文综述的目的是强调肾脏疾病中关键 miRNA 的发展,以及这将如何影响未来肾脏疾病患者的诊断和治疗。

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