Functional polarization of human hepatoma HepaRG cells in response to forskolin - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Scientific Reports Année : 2018

Functional polarization of human hepatoma HepaRG cells in response to forskolin

Résumé

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 mu M 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.
Fichier principal
Vignette du fichier
s41598-018-34421-8.pdf (2.56 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-01973693 , version 1 (15-07-2019)

Identifiants

Citer

Abdullah Mayati, Amelie Moreau, Marc Le Vée, Arnaud Bruyère, Elodie Jouan, et al.. Functional polarization of human hepatoma HepaRG cells in response to forskolin. Scientific Reports, 2018, 8 (1), pp.16115. ⟨10.1038/s41598-018-34421-8⟩. ⟨hal-01973693⟩
52 Consultations
98 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More