Urinary MicroRNA biomarkers of nephrotoxicity in Macaca fascicularis

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology Pub Date : 2024-06-25 DOI:10.1016/j.yrtph.2024.105668

Subham Dasgupta , Tatiana Sharapova , Prathap K. Mahalingaiah , Brian N. Chorley , Ahmed Shoieb , Takayuki Tsuji , Alef A.C. dos Santos , Rohit Chari , Ali Ebrahimi , Deidre A. Dalmas Wilk , Syril Pettit , Bhupinder Bawa , Erin Vaughan , Terry R. van Vleet , Constance A. Mitchell , Peter S.T. Yuen

{"title":"Urinary MicroRNA biomarkers of nephrotoxicity in Macaca fascicularis","authors":"Subham Dasgupta , Tatiana Sharapova , Prathap K. Mahalingaiah , Brian N. Chorley , Ahmed Shoieb , Takayuki Tsuji , Alef A.C. dos Santos , Rohit Chari , Ali Ebrahimi , Deidre A. Dalmas Wilk , Syril Pettit , Bhupinder Bawa , Erin Vaughan , Terry R. van Vleet , Constance A. Mitchell , Peter S.T. Yuen","doi":"10.1016/j.yrtph.2024.105668","DOIUrl":null,"url":null,"abstract":"<div><p>Drug-induced kidney injury (DIKI) refers to kidney damage resulting from the administration of medications. The aim of this project was to identify reliable urinary microRNA (miRNAs) biomarkers that can be used as potential predictors of DIKI before disease diagnosis. This study quantified a panel of six miRNAs (miRs-210-3p, 423-5p, 143-3p, 130b-3p, 486-5p, 193a-3p) across multiple time points using urinary samples from a previous investigation evaluating effects of a nephrotoxicant in cynomolgus monkeys. Exosome-associated miRNA exhibited distinctive trends when compared to miRNAs quantified in whole urine, which may reflect a different urinary excretion mechanism of miRNAs than those released passively into the urine. Although further research and mechanistic studies are required to elucidate how these miRNAs regulate signaling in disease pathways, we present, for the first time, data that several miRNAs displayed strong correlations with histopathology scores, thus indicating their potential use as biomarkers to predict the development of DIKI in preclinical studies and clinical trials. Also, these findings can potentially be translated into other non-clinical species or human for the detection of DIKI.</p></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"151 ","pages":"Article 105668"},"PeriodicalIF":3.0000,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0273230024001090/pdfft?md5=6baa7d7a0f5da3c6c450cf9c300bbd9b&pid=1-s2.0-S0273230024001090-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Regulatory Toxicology and Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0273230024001090","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, LEGAL","Score":null,"Total":0}

引用次数: 0

Abstract

Drug-induced kidney injury (DIKI) refers to kidney damage resulting from the administration of medications. The aim of this project was to identify reliable urinary microRNA (miRNAs) biomarkers that can be used as potential predictors of DIKI before disease diagnosis. This study quantified a panel of six miRNAs (miRs-210-3p, 423-5p, 143-3p, 130b-3p, 486-5p, 193a-3p) across multiple time points using urinary samples from a previous investigation evaluating effects of a nephrotoxicant in cynomolgus monkeys. Exosome-associated miRNA exhibited distinctive trends when compared to miRNAs quantified in whole urine, which may reflect a different urinary excretion mechanism of miRNAs than those released passively into the urine. Although further research and mechanistic studies are required to elucidate how these miRNAs regulate signaling in disease pathways, we present, for the first time, data that several miRNAs displayed strong correlations with histopathology scores, thus indicating their potential use as biomarkers to predict the development of DIKI in preclinical studies and clinical trials. Also, these findings can potentially be translated into other non-clinical species or human for the detection of DIKI.

查看原文本刊更多论文

猕猴肾毒性的尿微RNA生物标志物

药物性肾损伤（DIKI）是指服用药物导致的肾损伤。本项目旨在确定可靠的尿液微RNA（miRNA）生物标志物，这些标志物可在疾病诊断前用作DIKI的潜在预测因子。本研究利用先前评估一种肾毒性药物对绒毛猴影响的调查中获得的尿液样本，在多个时间点对六种 miRNA（miRs-210-3p、423-5p、143-3p、130b-3p、486-5p、193a-3p）进行了量化。与全尿中定量的 miRNA 相比，外泌体相关的 miRNA 表现出不同的趋势，这可能反映出 miRNA 的排泄机制与被动释放到尿液中的 miRNA 不同。虽然要阐明这些 miRNA 如何调控疾病通路中的信号转导，还需要进一步的研究和机理探讨，但我们首次发现了一些 miRNA 与组织病理学评分有很强的相关性，这表明在临床前研究和临床试验中，这些 miRNA 有可能被用作预测 DIKI 发病的生物标志物。此外，这些发现还有可能被转化到其他非临床物种或人类身上，用于检测 DIKI。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Regulatory Toxicology and Pharmacology 医学-毒理学

CiteScore

6.70

自引率

8.80%

发文量

147

审稿时长

58 days

期刊介绍： Regulatory Toxicology and Pharmacology publishes peer reviewed articles that involve the generation, evaluation, and interpretation of experimental animal and human data that are of direct importance and relevance for regulatory authorities with respect to toxicological and pharmacological regulations in society. All peer-reviewed articles that are published should be devoted to improve the protection of human health and environment. Reviews and discussions are welcomed that address legal and/or regulatory decisions with respect to risk assessment and management of toxicological and pharmacological compounds on a scientific basis. It addresses an international readership of scientists, risk assessors and managers, and other professionals active in the field of human and environmental health. Types of peer-reviewed articles published: -Original research articles of relevance for regulatory aspects covering aspects including, but not limited to: 1.Factors influencing human sensitivity 2.Exposure science related to risk assessment 3.Alternative toxicological test methods 4.Frameworks for evaluation and integration of data in regulatory evaluations 5.Harmonization across regulatory agencies 6.Read-across methods and evaluations -Contemporary Reviews on policy related Research issues -Letters to the Editor -Guest Editorials (by Invitation)