Herrera-Pérez Zeneida, Gretz Norbert, Dweep Harsh
Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Curr Genomics. 2016 Jun;17(3):279-93. doi: 10.2174/1389202917666160202220555.
Cisplatin (CDDP) is a well-known antineoplastic drug which has been extensively utilized over the last decades in the treatment of numerous kinds of tumors. However, CDDP induces a wide range of toxicities in a dose-dependent manner, among which nephrotoxicity is of particular importance. Still, the mechanism of CDDP-induced renal damage is not completely understood; moreover, the knowledge about the role of microRNAs (miRNAs) in the nephrotoxic response is still unknown. miRNAs are known to interact with the representative members of a diverse range of regulatory pathways (including postnatal development, proliferation, inflammation and fibrosis) and pathological conditions, including kidney diseases: polycystic kidney diseases (PKDs), diabetic nephropathy (DN), kidney cancer, and drug-induced kidney injury. In this review, we shed light on the following important aspects: (i) information on genes/proteins and their interactions with previously known pathways engaged with CDDP-induced nephrotoxicity, (ii) information on newly discovered biomarkers, especially, miRNAs for detecting CDDP-induced nephrotoxicity and (iii) information to improve our understanding on CDDP. This information will not only help the researchers belonging to nephrotoxicity field, but also supply an indisputable help for oncologists to better understand and manage the side effects induced by CDDP during cancer treatment. Moreover, we provide up-to-date information about different in vivo and in vitro models that have been utilized over the last decades to study CDDP-induced renal injury. Taken together, this review offers a comprehensive network on genes, miRNAs, pathways and animal models which will serve as a useful resource to understand the molecular mechanism of CDDP-induced nephrotoxicity.
顺铂（CDDP）是一种著名的抗肿瘤药物，在过去几十年中被广泛用于治疗多种肿瘤。然而，CDDP会以剂量依赖性方式引发多种毒性，其中肾毒性尤为重要。尽管如此，CDDP诱导肾损伤的机制尚未完全明确；此外，关于微小RNA（miRNA）在肾毒性反应中的作用仍不清楚。已知miRNA与多种调节途径（包括出生后发育、增殖、炎症和纤维化）以及病理状况（包括肾脏疾病：多囊肾病（PKD）、糖尿病肾病（DN）、肾癌和药物性肾损伤）的代表性成员相互作用。在本综述中，我们阐述了以下重要方面：（i）与CDDP诱导的肾毒性相关的基因/蛋白质及其与先前已知途径相互作用的信息，（ii）新发现的生物标志物的信息，特别是用于检测CDDP诱导的肾毒性的miRNA，以及（iii）有助于增进我们对CDDP理解的信息。这些信息不仅将帮助肾毒性领域的研究人员，还将为肿瘤学家更好地理解和管理癌症治疗期间CDDP诱导的副作用提供无可争议的帮助。此外，我们提供了过去几十年中用于研究CDDP诱导的肾损伤的不同体内和体外模型的最新信息。综上所述，本综述提供了一个关于基因、miRNA、途径和动物模型的综合网络，这将作为理解CDDP诱导肾毒性分子机制的有用资源。
