Current Chemical Genomics and Translational Medicine




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ISSN: ― Volume ,
RESEARCH ARTICLE

Development and Application of Human Renal Proximal Tubule Epithelial Cells for Assessment of Compound Toxicity



Shuaizhang Li1, Jinghua Zhao1, Ruili Huang1, Toni Steiner2, Maureen Bourner2, Michael Mitchell2, David C. Thompson2, Bin Zhao3, Menghang Xia1, *
1 9800 Medical Center Drive, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-3375, USA
2 Sigma-Aldrich Corporation, St. Louis, MO 63103, USA
3 Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 10085, China

Abstract

Kidney toxicity is a major problem both in drug development and clinical settings. It is difficult to predict nephrotoxicity in part because of the lack of appropriate in vitro cell models, limited endpoints, and the observation that the activity of membrane transporters which plays important roles in nephrotoxicity by affecting the pharmacokinetic profile of drugs is often not taken into account. We developed a new cell model using pseudo-immortalized human primary renal proximal tubule epithelial cells. This cell line (SA7K) was characterized by the presence of proximal tubule cell markers as well as several functional properties, including transporter activity and response to a few well-characterized nephrotoxicants. We subsequently evaluated a group of potential nephrotoxic compounds in SA7K cells and compared them to a commonly used human immortalized kidney cell line (HK-2). Cells were treated with test compounds and three endpoints were analyzed, including cell viability, apoptosis and mitochondrial membrane potential. The results showed that most of the known nephrotoxic compounds could be detected in one or more of these endpoints. There were sensitivity differences in response to several of the chemicals between HK-2 and SA7K cells, which may relate to differences in expressions of key transporters or other components of nephrotoxicity pathways. Our data suggest that SA7K cells appear as promising for the early detection of renal toxicants.

Keywords: Apoptosis, Mitochondrial membrane potential (MMP), Nephrotoxicity, SA7K cells, Transporters.

Article Information


Identifiers and Pagination:

Year: 2017
Volume: 11
First Page: 19
Last Page: 30
Publisher Id: CCGTM-11-19
DOI: 10.2174/2213988501711010019

Article History:

Received Date: 06/06/2016
Revision Received Date: 28/10/2016
Acceptance Date: 23/11/2016
Electronic publication date: 14/02/2017
Collection year: 2017

© 2017 Li et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at the 9800 Medical Center Drive, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892-3370 USA, Tel: 301-217-5718, E-mail: mxia@mail.nih.gov


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