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蛋白质组学和代谢组学在遗传性肾脏疾病研究中的应用:从大数据到精准医学

[Application of proteomics and metabolomics to study inherited kidney disorders: from big data to precision medicine].

作者信息

Cervesato Angela, Raucci Raffaele, Buononato Dario, Marchese Emanuela, Capolongo Giovanna, Perna Alessandra, Capasso Giovambattista, Zacchia Miriam

机构信息

Sezione di Nefrologia, Dipartimento di Scienze Mediche Traslazionali, Università degli Studi della Campania "L. Vanvitelli", Napoli, Italy.

Dipartimento di Salute Mentale e Fisica e Medicina Preventiva, Università degli Studi della Campania "L. Vanvitelli", Napoli, Italy.

出版信息

G Ital Nefrol. 2020 Dec 7;37(6):2020-vol6.

Abstract

The recent application of proteomics and metabolomics to clinical medicine has demonstrated their potential role in complementing genomics for a better understanding of diseases' patho-physiology. These technologies offer the clear opportunity to identify risk factors, disease-specific or stage-specific biomarkers and to predict therapeutic response. This article is an overview of the recent insights obtained by metabolomic and proteomic studies in inherited kidney disorders. Proteomics studies have allowed the definition of a detailed picture of protein composition, post-translational modifications and interactions in kidney-derived samples, improving our understanding of renal physiology, especially of tubular transport and primary cilium-related functions. Studies on patients' urine samples and experimental models of inherited kidney diseases have provided clues suggesting novel potential pathological mechanisms and biomarkers of disease, for example in polycystic kidney disease. Metabolomic-based studies have been recently applied to assess biological system disturbances caused by specific genetic mutations resulting in inherited kidney disorders. These studies have been mainly carried out on mouse and rat models of cystic and metabolic disorders (such as Fabry disease), and on patients' urine samples. They have provided a significant contribution in understanding disease pathophysiology, promoting the discovery of aberrant biochemical pathways and contributing to the development of targeted therapies.

摘要

蛋白质组学和代谢组学在临床医学中的最新应用已证明,它们在补充基因组学方面具有潜在作用,有助于更好地理解疾病的病理生理学。这些技术为识别风险因素、疾病特异性或阶段特异性生物标志物以及预测治疗反应提供了明确机会。本文概述了代谢组学和蛋白质组学研究在遗传性肾脏疾病方面取得的最新见解。蛋白质组学研究能够详细描绘肾脏来源样本中的蛋白质组成、翻译后修饰及相互作用,增进了我们对肾脏生理学的理解,尤其是对肾小管转运和初级纤毛相关功能的理解。对遗传性肾脏疾病患者尿液样本及实验模型的研究提供了线索,提示了新的潜在病理机制和疾病生物标志物,如在多囊肾病中。基于代谢组学的研究最近已应用于评估由导致遗传性肾脏疾病的特定基因突变引起的生物系统紊乱。这些研究主要在囊性和代谢性疾病(如法布里病)的小鼠和大鼠模型以及患者尿液样本上进行。它们在理解疾病病理生理学、促进异常生化途径的发现以及推动靶向治疗的发展方面做出了重大贡献。

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