Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: In total seven sncRNAs were negatively associated with prevalent DKD (all PFDR ≤ 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).
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: In total seven sncRNAs were negatively associated with prevalent DKD (all PFDR ≤ 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).
CONCLUSIONS: 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.
摘要：
背景：微血管和大血管并发症在2型糖尿病患者中很常见。最近，人们对研究循环的非编码小RNA（sncRNA）作为糖尿病并发症发展的贡献者的潜力越来越感兴趣。在这项研究中，我们调查了2型糖尿病患者中循环sncRNAs水平与糖尿病肾病（DKD）的相关性。
方法：使用小RNA-seq测定血浆sncRNAs水平，允许检测miRNAs，snoRNAs,piRNAs,tRNA片段，和各种其他sncRNA类。我们测试了2型糖尿病患者中差异表达的sncRNAs，有DKD（n=69）或无DKD（n=405）。在二级分析中，我们还测试了与eGFR的关联，白蛋白尿（UACR），和血浆蛋白质组。
结果：总共7个sncRNAs与普遍DKD呈负相关（所有PFDR≤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，七个sncRNAs，尤其是piRNApiR-019825，与24种蛋白质的血浆水平相关，其中一些已知与肾功能相关，包括TNFsR-I（TNFRFS1A），DAN(NBL1)和胱抑素C(CST3)。
结论：我们已经鉴定了新的非编码小RNA，主要来自microRNA以外的类，与糖尿病肾病有关。我们的结果表明，小的非编码RNA在DKD中的参与超出了已知的microRNA，并且还涉及其他类型的sncRNA，特别是snoRNA和piR-019825，以前从未与肾功能相关的研究。
方法：使用小RNA-seq测定血浆sncRNAs水平，允许检测miRNAs，snoRNAs,piRNAs,tRNA片段，和各种其他sncRNA类。我们测试了2型糖尿病患者中差异表达的sncRNAs，有DKD（n=69）或无DKD（n=405）。在二级分析中，我们还测试了与eGFR的关联，白蛋白尿（UACR），和血浆蛋白质组。
结果：总共7个sncRNAs与普遍DKD呈负相关（所有PFDR≤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，七个sncRNAs，尤其是piRNApiR-019825，与24种蛋白质的血浆水平相关，其中一些已知与肾功能相关，包括TNFsR-I（TNFRFS1A），DAN(NBL1)和胱抑素C(CST3)。
结论：我们已经鉴定了新的非编码小RNA，主要来自microRNA以外的类，与糖尿病肾病有关。我们的结果表明，小的非编码RNA在DKD中的参与超出了已知的microRNA，并且还涉及其他类型的sncRNA，特别是snoRNA和piR-019825，以前从未与肾功能相关的研究。
