ArticleScientific reports2018
Functional polarization of human hepatoma HepaRG cells in response to forskolin.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
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- Activation of the TGR5/cAMP/PKA/CREB axis in cholangiocytes mediates epithelial-mesenchymal transition and fibrosis in hepatolithiasis.Biology direct · 2026Article
- Computational integration of in vivo single cell and in vitro bulk transcriptomics across 236 human and mouse datasets differentiates physiological versus non-physiological hepatic cell lines for hepatotoxicity screening.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Context-dependent Activities of Mitrephorone Link Lipid Redirection, Anti-inflammatory Action, and Ferroptosis Control to Hepatocyte Protection.Theranostics · 2026Article
- The Evolution of Cell Culture Systems to Study Hepatitis B Virus Pathogenesis and Antiviral Susceptibility.Viruses · 2025Review
- Improved functionality of hepatic spheroids cultured in acoustic levitation compared to existing 2D and 3D models.Scientific reports · 2024Article
- Forskolin induces FXR expression and enhances maturation of iPSC-derived hepatocyte-like cells.Frontiers in cell and developmental biology · 2024Article
- Natural compounds targeting nuclear receptors for effective cancer therapy.Cancer metastasis reviews · 2023Review
- Cell Culture Systems for Studying Hepatitis B and Hepatitis D Virus Infections.Life (Basel, Switzerland) · 2023Review
- Three-Dimensional Cell Co-Culture Liver Models and Their Applications in Pharmaceutical Research.International journal of molecular sciences · 2023Review
- Immuno-inflammatoryFrontiers in immunology · 2023Article
- Harnessing conserved signaling and metabolic pathways to enhance the maturation of functional engineered tissues.NPJ Regenerative medicine · 2022Review
- Hepatic Models in Precision Medicine: An African Perspective on Pharmacovigilance.Frontiers in genetics · 2022Article
- DMSO-free highly differentiated HepaRG spheroids for chronic toxicity, liver functions and genotoxicity studies.Archives of toxicology · 2022Article
- Tight junction stabilization prevents HepaRG cell death in drug-induced intrahepatic cholestasis.Biology open · 2021Article
- Human Three-Dimensional Hepatic Models: Cell Type Variety and Corresponding Applications.Frontiers in bioengineering and biotechnology · 2021Review
- Article
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Authors and funding
8 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HepaRG is an original human hepatoma cell line, acquiring highly differentiated hepatic features when exposed to dimethylsulfoxide (DMSO). To search alternatives to DMSO, which may exert some toxicity, we have analyzed the effects of forskolin (FSK), a cAMP-generating agent known to favor differentiation of various cell types. FSK used at 50 µM for 3 days was found to promote polarization of high density-plated HepaRG cells, i.e., it markedly enhanced the formation of functional biliary canaliculi structures. It also increased expressions of various hepatic markers, including those of cytochrome P-450 (CYP) 3A4, of drug transporters like NTCP, OATP2B1 and BSEP, and of metabolism enzymes like glucose 6-phosphatase. In addition, FSK-treated HepaRG cells displayed enhanced activities of CYP3A4, NTCP and OATPs when compared to untreated cells. These polarizing/differentiating effects of FSK were next shown to reflect not only the generation of cAMP, but also the activation of the xenobiotic sensing receptors PXR and FXR by FSK. Co-treatment of HepaRG cells by the cAMP analog Sp-5,6-DCl-cBIMPS and the reference PXR agonist rifampicin reproduced the polarizing effects of FSK. Therefore, FSK may be considered as a relevant alternative to DMSO for getting polarized and differentiated HepaRG cells, notably for pharmacological and toxicological studies.
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