ArticleScientific reports2022
A novel differentiated HuH-7 cell model to examine bile acid metabolism, transport and cholestatic hepatotoxicity.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Hepatocyte Models for Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comparative Analysis of Non-HepG2 Cell Models.International journal of molecular sciences · 2026Review
- Dexamethasone-Mediated Regulation of CYP3A4 and UGTs in Human Hepatoma HuH-7 Cells.Fundamental & clinical pharmacology · 2026Article
- Evaluation of a human 3D multicellular hepatic spheroid model as a platform for studying hepatic transporters.Cellular and molecular life sciences : CMLS · 2025Article
- Novel emerging cell and organoid systems for the study of drug metabolism and toxicity in humans.Drug metabolism and disposition: the biological fate of chemicals · 2025Review
- Targeting the p38/MAPK pathway to induce apoptosis: a multidimensional mechanistic exploration of Mentha and its active compound diosmetin against liver cancer.Scientific reports · 2025Article
- Modeling of lung-liver interaction during infection in a human fluidic organ-on-a-chip.Scientific reports · 2025Article
- Visualization of CYP3A4 expression at both mRNA and protein levels simultaneously at single cell resolution in various conditions using RNAscope combined with immunofluorescence.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Decoding HuH-7: a comprehensive genetic and molecular portrait of a widely used hepatocellular carcinoma model.Frontiers in cell and developmental biology · 2025Article
- Development of anFrontiers in pharmacology · 2025Article
- Hepatic Bile Acid Transporters and Drug-induced Hepatotoxicity.Toxicologic pathology · 2023Review
- Review
- Effect of mTOR inhibitors on sodium taurocholate cotransporting polypeptide (NTCP) functionFrontiers in pharmacology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Hepatic cell lines serve as economical and reproducible alternatives for primary human hepatocytes. However, the utility of hepatic cell lines to examine bile acid homeostasis and cholestatic toxicity is limited due to abnormal expression and function of bile acid-metabolizing enzymes, transporters, and the absence of canalicular formation. We discovered that culturing HuH-7 human hepatoma cells with dexamethasone (DEX) and 0.5% dimethyl sulfoxide (DMSO) for two weeks, with Matrigel overlay after one week, resulted in a shorter and improved differentiation process. These culture conditions increased the expression and function of the major bile acid uptake and efflux transporters, sodium taurocholate co-transporting polypeptide (NTCP) and the bile salt export pump (BSEP), respectively, in two-week cultures of HuH-7 cells. This in vitro model was further characterized for expression and function of bile acid-metabolizing enzymes, transporters, and cellular bile acids. Differentiated HuH-7 cells displayed a marked shift in bile acid composition and induction of cytochrome P450 (CYP) 7A1, CYP8B1, CYP3A4, and bile acid-CoA: amino acid N-acyltransferase (BAAT) mRNAs compared to control. Inhibition of taurocholate uptake and excretion after a 24-h treatment with prototypical cholestatic drugs suggests that differentiated HuH-7 cells are a suitable model to examine cholestatic hepatotoxicity.
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