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微小RNA在实验性诱导的慢性肾病猫的血清和肾组织中差异表达:一项初步研究。

MicroRNAs are differentially expressed in the serum and renal tissues of cats with experimentally induced chronic kidney disease: a preliminary study.

作者信息

Grimes Janet A, Lourenço Bianca N, Coleman Amanda E, Rissi Daniel R, Schmiedt Chad W

机构信息

Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA.

Athens Veterinary Diagnostic Laboratory, Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA.

出版信息

Am J Vet Res. 2022 Mar 3;83(5):426-433. doi: 10.2460/ajvr.21.08.0136.

Abstract

OBJECTIVE

To identify differentially expressed microRNA in the serum and renal tissues of cats with experimentally induced chronic kidney disease (CKD).

SAMPLE

Banked renal tissues and serum from 4 cats.

PROCEDURES

Cats previously underwent 90-minute unilateral ischemia with delayed contralateral nephrectomy 3 months after ischemia. Tissues were collected from the contralateral kidney at the time of nephrectomy and from the ischemic kidney 6 months after nephrectomy (study end). Serum was collected prior to ischemia (baseline serum) and at study end (end point serum). Total RNA was isolated from tissues and serum, and microRNA sequencing was performed with differential expression analysis between the contralateral and ischemic kidney and baseline and end point serum.

RESULTS

20 microRNAs were differentially expressed between ischemic and contralateral kidneys, and 52 microRNAs were differentially expressed between end point and baseline serum. Five microRNAs were mutually differentially expressed between ischemic and contralateral kidneys and baseline and end point serum, with 4 (mir-21, mir-146, mir-199, and mir-235) having increased expression in both the ischemic kidney and end point serum and 1 (mir-382) having increased expression in the ischemic kidney and decreased expression in end point serum. Predicted target search for these microRNA revealed multiple genes previously shown to be involved in the pathogenesis of feline CKD, including hypoxia-inducible factor-1α, transforming growth factor-β, hepatocyte growth factor, fibronectin, and vascular endothelial growth factor A.

CLINICAL RELEVANCE

MicroRNAs were differentially expressed after CKD induction in this preliminary study. Regulation of renal fibrosis in feline CKD may occur through microRNA regulation of mRNAs of pro- and anti-fibrotic genes.

摘要

目的

鉴定实验性诱导的慢性肾病(CKD)猫血清和肾组织中差异表达的微小RNA。

样本

来自4只猫的储存肾组织和血清。

步骤

猫先前经历了90分钟的单侧缺血,并在缺血3个月后进行了延迟的对侧肾切除。在肾切除时从对侧肾收集组织,并在肾切除6个月后(研究结束时)从缺血肾收集组织。在缺血前(基线血清)和研究结束时(终点血清)收集血清。从组织和血清中分离总RNA,并进行微小RNA测序,分析对侧肾与缺血肾以及基线血清与终点血清之间的差异表达。

结果

缺血肾与对侧肾之间有20种微小RNA差异表达,终点血清与基线血清之间有52种微小RNA差异表达。缺血肾与对侧肾以及基线血清与终点血清之间有5种微小RNA相互差异表达,其中4种(mir-21、mir-146、mir-199和mir-235)在缺血肾和终点血清中表达均增加,1种(mir-382)在缺血肾中表达增加而在终点血清中表达降低。对这些微小RNA的预测靶标搜索显示,多个基因先前已被证明参与猫CKD的发病机制,包括缺氧诱导因子-1α、转化生长因子-β、肝细胞生长因子、纤连蛋白和血管内皮生长因子A。

临床意义

在这项初步研究中,CKD诱导后微小RNA存在差异表达。猫CKD中肾纤维化的调节可能通过微小RNA对促纤维化和抗纤维化基因mRNA的调节来实现。

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