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000126063 0247_ $$2doi$$a10.1016/j.tiv.2014.10.005
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000126063 0247_ $$2ISSN$$a0887-2333
000126063 0247_ $$2ISSN$$a1879-3177
000126063 037__ $$aDKFZ-2017-02178
000126063 041__ $$aeng
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000126063 1001_ $$aAschauer, Lydia$$b0
000126063 245__ $$aApplication of RPTEC/TERT1 cells for investigation of repeat dose nephrotoxicity: A transcriptomic study.
000126063 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2015
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000126063 520__ $$aThe kidney is a major target organ for toxicity. Incidence of chronic kidney disease (CKD) is increasing at an alarming rate due to factors such as increasing population age and increased prevalence of heart disease and diabetes. There is a major effort ongoing to develop superior predictive models of renal injury and early renal biomarkers that can predict onset of CKD. In the EU FP7 funded project, Predict-IV, we investigated the human renal proximal tubule cells line, RPTEC/TERT1 for their applicability to long term nephrotoxic mechanistic studies. To this end, we used a tiered strategy to optimise dosing regimes for 9 nephrotoxins. Our final testing protocol utilised differentiated RPTEC/TERT1 cells cultured on filter inserts treated with compounds at both the apical and basolateral side, at concentrations not exceeding IC10, for 14 days in a 24 h repeat application. Transepithelial electrical resistance and supernatant lactate were measured over the duration of the experiments and genome wide transcriptomic profiles were assayed at day 1, 3 and 14. The effect of hypoxia was investigated for a subset of compounds. The transcriptomic data were analysed to investigate compound-specific effects, global responses and mechanistically informative signatures. In addition, several potential clinically useful renal injury biomarkers were identified.
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000126063 650_7 $$2NLM Chemicals$$aLactates
000126063 650_7 $$2NLM Chemicals$$aPharmaceutical Preparations
000126063 7001_ $$aLimonciel, Alice$$b1
000126063 7001_ $$aWilmes, Anja$$b2
000126063 7001_ $$0P:(DE-HGF)0$$aStanzel, Sven$$b3
000126063 7001_ $$0P:(DE-He78)bb6a7a70f976eb8df1769944bf913596$$aKopp-Schneider, Annette$$b4$$udkfz
000126063 7001_ $$aHewitt, Philip$$b5
000126063 7001_ $$aLukas, Arno$$b6
000126063 7001_ $$aLeonard, Martin O$$b7
000126063 7001_ $$aPfaller, Walter$$b8
000126063 7001_ $$aJennings, Paul$$b9
000126063 773__ $$0PERI:(DE-600)1501079-x$$a10.1016/j.tiv.2014.10.005$$gVol. 30, no. 1 Pt A, p. 106 - 116$$n1 Pt A$$p106 - 116$$tToxicology in vitro$$v30$$x0887-2333$$y2015
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000126063 9141_ $$y2015
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