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尿酸结石患者微小RNA表达分析。

Analysis of microRNA expression in patients with uric acid calculi.

作者信息

Reis Sabrina T, Simões William M, Romão Poliana, Candido Patrícia, Zampolli Lucca J, Guimarães Vanessa R, Ayres Daniel, Pimenta Ruan, Leite Katia Ramos Moreira, Nahas William C, Mazzucchi Eduardo

机构信息

Laboratório de Investigação Médica 55 (LIM55), Faculdade de Medicina, Hospital das Clínicas HCFMUSP, Universidade de São Paulo, Av. Dr. Arnaldo 455, 2° floor, room 2145 - Cerqueira Cesar, São Paulo, SP, 01246-903, Brazil.

Moriah Institute of Science and Education (MISE), Hospital Moriah, Sao Paulo, Brazil.

出版信息

Urolithiasis. 2025 Apr 5;53(1):66. doi: 10.1007/s00240-025-01736-x.

Abstract

Uric acid calculi (UAC) account for about 10% of cases worldwide, although this varies among countries. The etiology of nephrolithiasis is multifactorial, involving both genetic and environmental factors. Kidney stones occur three times more frequently in individuals with a family history of the condition compared to those without such a history. Genetic factors also contribute to cases of UAC. Genes such as ZNF365, SLC2A9 and SLC22A12 may be associated with the development of uric acid stones. MicroRNAs (miRNAs) are small RNA molecules, that play a significant role in regulating gene expression. The aim of this study was to characterize the expression profile of miRNAs associated with the SLC2A9, SLC22A12 and ZNF365 genes in patients with uric lithiasis. Twenty-two patients with pure uric stones and 8 controls with no history of lithiasis were included, all of whom consented voluntarily. To analyze the gene expression levels of the microRNAs studied, total RNA was obtained using the miRVanamiRNA kit, following the manufacturer's guidelines. qPCR analyses were then carried out using specific probes for the selected microRNAs. When comparing clinical characteristics, patients with nephrolithiasis had significant hyperuricemia (p < 0.0001) and more acidic urine (p = 0.0012). Lower urinary citrate excretion was also observed in patients with nephrolithiasis (p = 0.0047). With regard to microRNA expression data, statistically significant under-expression was observed in patients with calculi of microRNAs 143-3p (p = 0.015), 4770 (p = 0.0194), 4750-3p (p = 0.037), 301b-5p (p = < 0.0001) and 9-5p (p = 0.0015). In addition, microRNAs 4770 and 4750-3p were underexpressed in individuals with multiple stones (p = 0.0197, p = 0.0023 respectively). In relation to miR-4750-3p, it was also overexpressed in cases with stones larger than 2 cm (p = 0.0557). With the results of our study, we can conclude that the microRNAs 143-3p, 4770, 4750-3p, 301b-5p and 9-5p may be associated with the development of uric lithiasis. In addition, under-expression of microRNAs 4770 and 4750-3p is associated with the occurrence of multiple stones, while over-expression of miR-4750-3p is related to the formation of stones larger than 2 cm.

摘要

尿酸结石(UAC)在全球病例中约占10%,不过各国情况有所不同。肾结石的病因是多因素的,涉及遗传和环境因素。有肾结石家族史的个体患肾结石的频率是无家族史个体的三倍。遗传因素也导致了尿酸结石病例的发生。诸如锌指蛋白365(ZNF365)、溶质载体家族2成员9(SLC2A9)和溶质载体家族22成员12(SLC22A12)等基因可能与尿酸结石的形成有关。微小RNA(miRNA)是小RNA分子,在调节基因表达中起重要作用。本研究的目的是描述尿酸结石患者中与SLC2A9、SLC22A12和ZNF365基因相关的miRNA表达谱。纳入了22例纯尿酸结石患者和8例无结石病史的对照者,所有患者均自愿同意参与。为了分析所研究的微小RNA的基因表达水平,按照制造商的说明使用miRVa纳米微小RNA试剂盒获取总RNA。然后使用针对所选微小RNA的特异性探针进行定量聚合酶链反应(qPCR)分析。在比较临床特征时,肾结石患者有显著的高尿酸血症(p < 0.0001)和尿液更偏酸性(p = 0.0012)。肾结石患者的尿枸橼酸盐排泄也较低(p = 0.0047)。关于微小RNA表达数据,在结石患者中观察到微小RNA 143 - 3p(p = 0.015)、4770(p = 0.0194)、4750 - 3p(p = 0.037)、301b - 5p(p = < 0.0001)和9 - 5p(p = 0.0015)有统计学意义的低表达。此外,微小RNA 4770和4750 - 3p在多发结石个体中表达下调(分别为p = 0.0197,p = 0.0023)。关于miR - 4750 - 3p,在结石大于2厘米的病例中也有过表达(p = 0.0557)。根据我们的研究结果,可以得出结论,微小RNA 143 - 3p、4770、4750 - 3p、301b - 5p和9 - 5p可能与尿酸结石的形成有关。此外,微小RNA 4770和4750 - 3p的低表达与多发结石的发生有关,而miR - 4750 - 3p的过表达与大于2厘米结石的形成有关。

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