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. 2019 Aug;96(2):158–167. doi: 10.1124/mol.118.114827

Fig. 2.

Fig. 2.

(A) Bile acid transport in the liver is mediated by various transporters functioning on both the canalicular and basolateral membranes of hepatocytes that efflux bile acids or phosphatidylcholine. Genes with polymorphic variants associated with clinical transaminitis are highlighted in green. In Huh7 cells, (B) 25 nM mithramycin was minimally cytotoxic and (C) affected the expression of several transporters. (D) CDCA upregulated ABCB4 in Huh7 cells regardless of the presence of mithramycin, whereas both TCA and CDCA upregulated ABCB11, which was inhibited by mithramycin. In HepaRG and HepaRG BSEP (−/−) cells, (E) mithramycin downregulated 6/11 and 8/11 bile transporters, respectively. (F) CDCA caused downregulation of ABCB4 and upregulation of ABCB11 in HepaRG cells. Mithramycin further reduced the expression of ABCB4 and ABCB11, while interrupting the inducibility of ABCB11. (G) Expression of other transporters was also altered by administration of mithramycin and CDCA. *P < 0.05; **P < 0.01; ***P < 0.001; and ****P < 0.0001. ns, non-significant.