Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Epidemiology and Data Sciences, Amsterdam University Medical Center, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Endocrine. 2024 Oct;86(1):194-203. doi: 10.1007/s12020-024-03884-3. Epub 2024 May 27.
Micro- and macrovascular complications are common among persons with type 2 diabetes. Recently there has been growing interest to investigate the potential of circulating small non-coding RNAs (sncRNAs) as contributors to the development of diabetic complications. In this study we investigate to what extent circulating sncRNAs levels associate with prevalent diabetic kidney disease (DKD) in persons with type 2 diabetes.
Plasma sncRNAs levels were determined using small RNA-seq, allowing detection of miRNAs, snoRNAs, piRNAs, tRNA fragments, and various other sncRNA classes. We tested for differentially expressed sncRNAs in persons with type 2 diabetes, with DKD (n = 69) or without DKD (n = 405). In secondary analyses, we also tested the association with eGFR, albuminuria (UACR), and the plasma proteome.
In total seven sncRNAs were negatively associated with prevalent DKD (all P ≤ 0.05). Including one microRNA (miR-143-5p), five snoRNAs (U8, SNORD118, SNORD24, SNORD107, SNORD87) and a piRNA (piR-019825 | DQ597218). Proteomic analyses showed that the seven sncRNAs, and especially the piRNA piR-019825, were associated with plasma levels of 24 proteins of which several have known associations with kidney function including TNF sR-I (TNFRFS1A), DAN (NBL1) and cystatin C (CST3).
We have identified novel small non-coding RNAs, primarily from classes other than microRNAs, that are associated with diabetic kidney disease. Our results show that the involvement of small non-coding RNAs in DKD goes beyond the already known microRNAs and also involves other classes of sncRNA, in particular snoRNAs and the piRNA piR-019825, that have never been studied before in relation to kidney function.
2 型糖尿病患者常见微血管和大血管并发症。最近，人们越来越关注循环小非编码 RNA（sncRNA）作为糖尿病并发症发展的潜在贡献者。在这项研究中，我们调查了循环 sncRNA 水平与 2 型糖尿病患者中常见的糖尿病肾病（DKD）的关联程度。
使用小 RNA-seq 测定血浆 sncRNA 水平，允许检测 miRNA、snoRNA、piRNA、tRNA 片段和各种其他 sncRNA 类别。我们在 2 型糖尿病患者中检测了有或没有 DKD（n=69）的差异表达 sncRNA。在二次分析中，我们还测试了与 eGFR、白蛋白尿（UACR）和血浆蛋白质组的关联。
共有七种 sncRNA 与 DKD 的存在呈负相关（均 P≤0.05）。包括一个 microRNA（miR-143-5p）、五个 snoRNA（U8、SNORD118、SNORD24、SNORD107、SNORD87）和一个 piRNA（piR-019825 | DQ597218）。蛋白质组学分析表明，这七种 sncRNA，特别是 piRNA piR-019825，与 24 种蛋白质的血浆水平相关，其中一些与肾功能相关，包括 TNF sR-I（TNFRFS1A）、DAN（NBL1）和胱抑素 C（CST3）。
我们已经确定了与糖尿病肾病相关的新型小非编码 RNA，主要来自于 miRNA 以外的其他类别。我们的结果表明，小非编码 RNA 参与 DKD 不仅超出了已知的 microRNA，还涉及 snoRNA 和 piRNA piR-019825 等其他 sncRNA 类别，这些类别以前从未在与肾功能有关的研究中研究过。
