Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, the Netherlands.
Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Nat Rev Nephrol. 2023 Sep;19(9):573-586. doi: 10.1038/s41581-023-00725-w. Epub 2023 Jun 7.
Post-transcriptional regulation by non-coding RNAs (ncRNAs) can modulate the expression of genes involved in kidney physiology and disease. A large variety of ncRNA species exist, including microRNAs, long non-coding RNAs, piwi-interacting RNAs, small nucleolar RNAs, circular RNAs and yRNAs. Despite early assumptions that some of these species may exist as by-products of cell or tissue injury, a growing body of literature suggests that these ncRNAs are functional and participate in a variety of processes. Although they function intracellularly, ncRNAs are also present in the circulation, where they are carried by extracellular vesicles, ribonucleoprotein complexes or lipoprotein complexes such as HDL. These systemic, circulating ncRNAs are derived from specific cell types and can be directly transferred to a variety of cells, including endothelial cells of the vasculature and virtually any cell type in the kidney, thereby affecting the function of the host cell and/or its response to injury. Moreover, chronic kidney disease itself, as well as injury states associated with transplantation and allograft dysfunction, is associated with a shift in the distribution of circulating ncRNAs. These findings may provide opportunities for the identification of biomarkers with which to monitor disease progression and/or the development of therapeutic interventions.
非编码 RNA（ncRNA）的转录后调控可以调节参与肾脏生理和疾病的基因的表达。存在大量的 ncRNA 种类，包括 microRNAs、长非编码 RNA、piwi 相互作用 RNA、小核仁 RNA、环状 RNA 和 yRNA。尽管早期的假设认为这些物种中的一些可能是细胞或组织损伤的副产品，但越来越多的文献表明这些 ncRNA 是具有功能的，并参与了多种过程。尽管它们在细胞内发挥作用，但 ncRNA 也存在于循环中，它们可以通过细胞外囊泡、核糖核蛋白复合物或脂蛋白复合物（如高密度脂蛋白）携带。这些系统的、循环的 ncRNA 来自特定的细胞类型，可以直接转移到多种细胞中，包括血管内皮细胞和肾脏中的几乎任何细胞类型，从而影响宿主细胞的功能和/或其对损伤的反应。此外，慢性肾脏病本身以及与移植和同种异体移植物功能障碍相关的损伤状态，与循环 ncRNA 分布的改变有关。这些发现可能为识别生物标志物提供机会，以便监测疾病进展和/或治疗干预的发展。
