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蛋白质组学标志物在肾脏病学中的应用:从动物模型到临床应用?

Implementation of Proteomics Biomarkers in Nephrology: From Animal Models to Human Application?

机构信息

Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France.

Université Toulouse III Paul-Sabatier, Toulouse, France.

出版信息

Proteomics Clin Appl. 2019 Mar;13(2):e1800089. doi: 10.1002/prca.201800089. Epub 2018 Nov 12.

Abstract

Preclinical animal models are extensively used in nephrology. In this review, the utility of performing proteome analysis of kidney tissue or urine in such models and transfer of the results to human application has been assessed. Analysis of the literature identified 68 relevant publications. Pathway analysis of the reported proteins clearly indicated links with known biological processes in kidney disease providing validation of the observed changes in the preclinical models. However, although most studies focused on the identification of early markers of kidney disease or prediction of its progression, none of the identified makers has made it to substantial validation in the clinic or at least in human samples. Especially in renal disease where urine is an abundant source of biomarkers of diseases of the kidney and the urinary tract, it therefore appears that the focus should be on human material based discovery studies. In contrast, the most valid information of proteome analysis of preclinical models in nephrology for translation in human disease resides in studies focusing on drug evaluation, both efficacy for translation to the clinic and for mechanistic insight.

摘要

临床前动物模型在肾脏病学中被广泛应用。本文评估了在这些模型中对肾脏组织或尿液进行蛋白质组分析,并将结果转化为临床应用的实用性。分析文献后确定了 68 篇相关出版物。对报告蛋白的途径分析清楚地表明与肾脏疾病中已知的生物学过程有关,从而验证了临床前模型中观察到的变化。然而,尽管大多数研究都集中在鉴定肾脏疾病的早期标志物或预测其进展,但没有一种鉴定出的标志物在临床上或至少在人体样本中得到实质性验证。特别是在肾脏疾病中,尿液是肾脏和泌尿道疾病生物标志物的丰富来源,因此,似乎应该将重点放在基于人体材料的发现研究上。相比之下,临床前肾脏病模型蛋白质组分析中对人类疾病最有转化价值的信息在于药物评估研究,包括对临床疗效的评估以及对机制的深入了解。

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