Expression profiles of urine exosomal tRNA-derived small RNAs and their potential roles in calcium oxalate stone disease.

IF 1.7 Q2 MEDICINE, GENERAL & INTERNAL Annals of Medicine and Surgery Pub Date : 2024-09-10 eCollection Date: 2024-10-01 DOI:10.1097/MS9.0000000000002563
Sen-Yuan Hong, Lin-Tao Miao, Yuan-Yuan Yang, Shao-Gang Wang
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Abstract

Background and objective: Exosomes have been confirmed to be implicated in the pathogenesis of calcium oxalate (CaOx) stones. tRNA-derived small RNAs (tsRNAs) are among the oldest small RNAs involved in exosome-mediated intercellular communication, yet their role in kidney stones remains unexplored. This pilot study aimed to identify differentially expressed tsRNAs (DEtsRNAs) in urine exosomes between CaOx stone patients and healthy controls and explore their potential roles in nephrolithiasis.

Method: First-morning urine samples were collected from three CaOx stone patients and three healthy controls. Urinary exosomes were isolated and analyzed by high-throughput sequencing to generate the expression profiles of tsRNAs and detect DEtsRNAs. Predicted target genes of DEtsRNAs were subjected to functional enrichment analysis. The authors also combined the public dataset GSE73680 to investigate how DEtsRNAs were related to stone formation.

Results: Four DEtsRNAs were significantly upregulated in CaOx stone patients compared to healthy controls. tRF-Lys-TTT-5005c was the most elevated, followed by tRF-Lys-CTT-5006c, tRF-Ala-AGC-5017b, and tRF-Gly-CCC-5004b. Bioinformatics analysis indicated that these four types of DEtsRNAs might serve distinct biological functions. Combined with data mining from the public dataset GSE73680, the authors assumed that exosomes carrying tRF-Lys-TTT-5005c and tRF-Lys-CTT-5006c could inhibit the expression of SMAD6, FBN1, and FZD1, thereby activating the BMP signaling pathway, which might induce an osteogenic-like transformation in target cells, resulting in the formation of Randall's plaques and CaOx stones.

Conclusion: The authors' findings shed light on the potential roles of tsRNAs in the pathogenesis of CaOx stone disease, highlighting exosomal DEtsRNAs as promising diagnostic biomarkers and therapeutic targets in nephrolithiasis.

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尿液外泌体 tRNA 衍生小 RNA 的表达谱及其在草酸钙结石病中的潜在作用。
背景和目的:tRNA衍生的小RNAs(tsRNAs)是参与外泌体介导的细胞间通讯的最古老的小RNAs之一,但它们在肾结石中的作用仍有待探索。这项试验性研究旨在鉴定钙结石患者和健康对照组尿液外泌体中不同表达的tsRNAs(DEtsRNAs),并探索它们在肾结石中的潜在作用:方法:收集三名 CaOx 结石患者和三名健康对照者的晨尿样本。方法:采集三名钙结石患者和三名健康对照者的清晨尿液样本,分离尿液外泌体并进行高通量测序分析,以生成 tsRNAs 的表达谱并检测 DEtsRNAs。对预测的 DEtsRNAs 靶基因进行了功能富集分析。作者还结合公共数据集GSE73680研究了DEtsRNA与结石形成的关系:tRF-Lys-TTT-5005c升高幅度最大,其次是tRF-Lys-CTT-5006c、tRF-Ala-AGC-5017b和tRF-Gly-CCC-5004b。生物信息学分析表明,这四类DEtsRNA可能具有不同的生物学功能。结合公共数据集 GSE73680 的数据挖掘,作者推测携带 tRF-Lys-TTT-5005c 和 tRF-Lys-CTT-5006c 的外泌体可以抑制 SMAD6、FBN1 和 FZD1 的表达,从而激活 BMP 信号通路,这可能会诱导靶细胞发生成骨样转化,导致兰德尔斑块和 CaOx 结石的形成:作者的研究结果揭示了tsRNAs在钙磷结石发病机制中的潜在作用,突出了外泌体DEtsRNAs作为肾炎诊断生物标志物和治疗靶点的前景。
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来源期刊
Annals of Medicine and Surgery
Annals of Medicine and Surgery MEDICINE, GENERAL & INTERNAL-
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5.90%
发文量
1665
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