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尿 miR-21 作为高血压肾损伤和纤维化的潜在生物标志物。

Urinary miR-21 as a potential biomarker of hypertensive kidney injury and fibrosis.

机构信息

Chinese-American Research Institute for Pediatrics & Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Department of Pharmaceutical Sciences, Wenzhou Medical University, Chashan University-town, Wenzhou, Zhejiang, China.

出版信息

Sci Rep. 2017 Dec 18;7(1):17737. doi: 10.1038/s41598-017-18175-3.

Abstract

Kidney biopsy is considered the golden criterion for diagnosing the etiology of kidney disease but accompanied by non-negligible complications. We explored the possibility of using urinary microRNA (miRNA) as a non-invasive biomarker for hypertensive kidney injury. We assessed differential miRNA expressions in the kidneys and urine of hypertensive mice with kidney injury induced by deoxycorticosterone acetate (DOCA)-salt compared to the controls. DOCA-salt treatment significantly increased renal tubular lesions from day 2 and mRNA expression of fibrosis-related genes from day 4 compared to the controls, respectively. Urinary albumin and N-acetyl-beta-D-glucosaminidase was significantly increased on day 8 compared to the controls. Array results showed that 20 out of 585 miRNAs were highly expressed in the kidneys and significantly increased on day 8 compared to the controls, including miR-21, miR-146b, miR-155 and miR-132, which were confirmed by real-time polymerase chain reaction and were significantly higher from day 4. The miR-21/creatinine in the urine from day 4 was significantly higher than that of the controls and was detected earlier than urinary albumin. In conclusion, we have identified urinary miR-21 that correlates with histopathological lesions and functional markers of kidney damage to facilitate a potential noninvasive detection for hypertensive kidney injury.

摘要

肾活检被认为是诊断肾脏疾病病因的金标准,但伴有不可忽视的并发症。我们探讨了使用尿 microRNA(miRNA)作为高血压性肾损伤的非侵入性生物标志物的可能性。我们评估了与对照组相比,由醛固酮(DOCA)-盐诱导的高血压小鼠肾脏和尿液中差异 miRNA 表达。与对照组相比,DOCA-盐处理分别在第 2 天和第 4 天显著增加了肾小管病变和纤维化相关基因的 mRNA 表达。与对照组相比,第 8 天尿白蛋白和 N-乙酰-β-D-氨基葡萄糖苷酶显著增加。阵列结果显示,在肾脏中高度表达的 585 个 miRNA 中有 20 个在第 8 天与对照组相比显著增加,包括 miR-21、miR-146b、miR-155 和 miR-132,通过实时聚合酶链反应证实,从第 4 天开始显著升高。第 4 天尿中的 miR-21/肌酐明显高于对照组,且早于尿白蛋白检测到。总之,我们已经确定了与组织病理学病变和肾功能标志物相关的尿 miR-21,以促进对高血压性肾损伤的潜在非侵入性检测。

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