Small RNA sequencing reveals snoRNAs and piRNA-019825 as novel players in diabetic kidney disease.

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM Endocrine Pub Date : 2024-10-01 Epub Date: 2024-05-27 DOI:10.1007/s12020-024-03884-3

L M 't Hart, J A de Klerk, G A Bouland, J H D Peerlings, M T Blom, S J Cramer, R Bijkerk, J W J Beulens, R C Slieker

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Abstract

Introduction: 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 P_FDR ≤ 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).

Conclusion: 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.

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小 RNA 测序发现 snoRNA 和 piRNA-019825 是糖尿病肾病的新型参与者。

导言：微血管和大血管并发症在 2 型糖尿病患者中很常见。最近，人们对循环小非编码 RNA（sncRNA）作为糖尿病并发症的潜在诱因的研究兴趣日益浓厚。在这项研究中，我们调查了循环 sncRNAs 水平与 2 型糖尿病患者糖尿病肾病（DKD）发病率的关联程度：血浆中的 sncRNAs 水平是通过小 RNA-seq 来确定的，可以检测 miRNAs、snoRNAs、piRNAs、tRNA 片段和其他各种 sncRNA 类别。我们检测了患有 DKD（69 人）或未患有 DKD（405 人）的 2 型糖尿病患者体内不同表达的 sncRNA。在辅助分析中，我们还检测了与eGFR、白蛋白尿（UACR）和血浆蛋白质组的关联：结果：共有 7 个 sncRNA 与流行性 DKD 呈负相关（所有 PFDR 均小于 0.05）。包括1个microRNA（miR-143-5p）、5个snoRNA（U8、SNORD118、SNORD24、SNORD107、SNORD87）和1个piRNA（piR-019825 | DQ597218）。蛋白质组分析表明，这 7 个 sncRNA，尤其是 piRNA piR-019825 与 24 种蛋白质的血浆水平有关，其中有几种蛋白质与肾功能有关，包括 TNF sR-I (TNFRFS1A)、DAN (NBL1) 和胱抑素 C (CST3)：结论：我们发现了与糖尿病肾病相关的新型小非编码 RNA，主要来自 microRNA 以外的其他类别。我们的研究结果表明，小非编码 RNA 在 DKD 中的参与超出了已知的 microRNA，还涉及到其他类别的 sncRNA，特别是 snoRNA 和 piRNA piR-019825，而之前从未研究过它们与肾功能的关系。

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来源期刊

Endocrine ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

5.40%

发文量

295

审稿时长

1.5 months

期刊介绍： Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.