ArticleToxicological sciences : an official journal of the Society of Toxicology2015
Comparative Localization and Functional Activity of the Main Hepatobiliary Transporters in HepaRG Cells and Primary Human Hepatocytes.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 73 citations in OpenAlex.
- How Polyphenol Metabolites Spatiotemporally Reprogram Transcription Factors and Human Proteostasis: A Metabolite-Centric Framework.Current issues in molecular biology · 2026Review
- Comparative DNA damage induced by eight nitrosamines in primary human and macaque hepatocytes.Chemico-biological interactions · 2025Article
- Cell-based approaches for the mechanistic understanding of drug-induced cholestatic liver injury.Archives of toxicology · 2025Review
- Mutation accumulation following extended exposure of human HepaRG cells to a genotoxic carcinogen.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2025Article
- Application of HepaRG cells for genotoxicity assessment: a review.Journal of environmental science and health. Part C, Toxicology and carcinogenesis · 2024Review
- Culture methods focusing on bile canalicular formation using primary human hepatocytes in a short time.In vitro cellular & developmental biology. Animal · 2023Article
- Inhibition of canalicular and sinusoidal taurocholate efflux by cholestatic drugs in human hepatoma HepaRG cells.Biopharmaceutics & drug disposition · 2022Article
- 3D cell culture models: Drug pharmacokinetics, safety assessment, and regulatory consideration.Clinical and translational science · 2021Review
- From street to lab: in vitro hepatotoxicity of buphedrone, butylone and 3,4-DMMC.Archives of toxicology · 2021Article
- Prospect ofFrontiers in toxicology · 2021Review
- Impairment of bile acid metabolism by perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in human HepaRG hepatoma cells.Archives of toxicology · 2020Article
- Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury.Archives of toxicology · 2020Article
- ZIP14 is degraded in response to manganese exposure.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2019Article
- Optimization of Canalicular ABC Transporter Function in HuH-7 Cells by Modification of Culture Conditions.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Protein expression and function of organic anion transporters in short-term and long-term cultures of Huh7 human hepatoma cells.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2019Article
- Evaluation of Drug Biliary Excretion Using Sandwich-Cultured Human Hepatocytes.European journal of drug metabolism and pharmacokinetics · 2019Review
- A Change in Bile Flow: Looking Beyond Transporter Inhibition in the Development of Drug-induced Cholestasis.Current drug metabolism · 2019Review
- mRNA Expression and Activity of Nucleoside Transporters in Human Hepatoma HepaRG Cells.Pharmaceutics · 2018Article
- Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures.Archives of toxicology · 2018Article
- Bioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applications.Genes · 2018Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of hepatobiliary transporters in drug-induced liver injury remains poorly understood. Various in vivo and in vitro biological approaches are currently used for studying hepatic transporters; however, appropriate localization and functional activity of these transporters are essential for normal biliary flow and drug transport. Human hepatocytes (HHs) are considered as the most suitable in vitro cell model but erratic availability and inter-donor functional variations limit their use. In this work, we aimed to compare localization of influx and efflux transporters and their functional activity in differentiated human HepaRG hepatocytes with fresh HHs in conventional (CCHH) and sandwich (SCHH) cultures. All tested influx and efflux transporters were correctly localized to canalicular [bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), multidrug resistance protein 1 (MDR1), and MDR3] or basolateral [Na(+)-taurocholate co-transporting polypeptide (NTCP) and MRP3] membrane domains and were functional in all models. Contrary to other transporters, NTCP and BSEP were less abundant and active in HepaRG cells, cellular uptake of taurocholate was 2.2- and 1.4-fold and bile excretion index 2.8- and 2.6-fold lower, than in SCHHs and CCHHs, respectively. However, when taurocholate canalicular efflux was evaluated in standard and divalent cation-free conditions in buffers or cell lysates, the difference between the three models did not exceed 9.3%. Interestingly, cell imaging showed higher bile canaliculi contraction/relaxation activity in HepaRG hepatocytes and larger bile canaliculi networks in SCHHs. Altogether, our results bring new insights in mechanisms involved in bile acids accumulation and excretion in HHs and suggest that HepaRG cells represent a suitable model for studying hepatobiliary transporters and drug-induced cholestasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.