TY  - JOUR
AU  - Aschauer, Lydia
AU  - Limonciel, Alice
AU  - Wilmes, Anja
AU  - Stanzel, Sven
AU  - Kopp-Schneider, Annette
AU  - Hewitt, Philip
AU  - Lukas, Arno
AU  - Leonard, Martin O
AU  - Pfaller, Walter
AU  - Jennings, Paul
TI  - Application of RPTEC/TERT1 cells for investigation of repeat dose nephrotoxicity: A transcriptomic study.
JO  - Toxicology in vitro
VL  - 30
IS  - 1 Pt A
SN  - 0887-2333
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - DKFZ-2017-02178
SP  - 106 - 116
PY  - 2015
AB  - The kidney is a major target organ for toxicity. Incidence of chronic kidney disease (CKD) is increasing at an alarming rate due to factors such as increasing population age and increased prevalence of heart disease and diabetes. There is a major effort ongoing to develop superior predictive models of renal injury and early renal biomarkers that can predict onset of CKD. In the EU FP7 funded project, Predict-IV, we investigated the human renal proximal tubule cells line, RPTEC/TERT1 for their applicability to long term nephrotoxic mechanistic studies. To this end, we used a tiered strategy to optimise dosing regimes for 9 nephrotoxins. Our final testing protocol utilised differentiated RPTEC/TERT1 cells cultured on filter inserts treated with compounds at both the apical and basolateral side, at concentrations not exceeding IC10, for 14 days in a 24 h repeat application. Transepithelial electrical resistance and supernatant lactate were measured over the duration of the experiments and genome wide transcriptomic profiles were assayed at day 1, 3 and 14. The effect of hypoxia was investigated for a subset of compounds. The transcriptomic data were analysed to investigate compound-specific effects, global responses and mechanistically informative signatures. In addition, several potential clinically useful renal injury biomarkers were identified.
KW  - Lactates (NLM Chemicals)
KW  - Pharmaceutical Preparations (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25450743
DO  - DOI:10.1016/j.tiv.2014.10.005
UR  - https://inrepo02.dkfz.de/record/126063
ER  -