Fig. 6: Bile acid overload-induced p53 nuclear translocation promotes the production of exosomes from hepatocytes.

a Quantitative real-time PCR of mature miR-194 in cultured rat Kupffer cells, stellate cells, hepatocytes, and PMVECs at 24 h after treatment with bile acid (GCDC, 50 μmol) (n = 5). Data are presented as the mean ± SD. *p < 0.05, compared with the control group. b Levels of miR-194 expression in exosomes from in vitro cultured rat primary hepatocytes and PMVECs cell culture medium at 24 h after treatment with bile acid (GCDC, 50 μmol) (n = 8). Data are represented as mean ± SD. *p < 0.05, compared with the control group. c Levels of miR-194 expression in PMVECs at 24 h after treatment with bile acid or hepatocyte-derived exosomes or both (n = 8). Data are presented as the mean ± SD. *p < 0.05, compared with the control group. d p53 was upregulated and translocated to the nucleus after bile acid treatment. Endogenous p53 in both the cytoplasm (non-NE) and nucleus (NE) of hepatocytes, which were treated with bile acid for different time point, was detected using anti-p53, β-actin, and lamin B antibodies for Western blotting (n = 8). Data are presented as the mean ± SD. *p < 0.05, compared with 0 h. e Levels of miR-194 expression in exosomes from in vitro cultured rat primary hepatocytes after which were treated with bile acid and 10 μM GW4869, 10 μM pifithrin-μ, P53 RNAi, NC RNAi for 24 h (n = 5). *p < 0.05, compared with the control group. ^#p < 0.05 compared with the BA group. f Levels of miR-194 expression in serum exosomes in the sham, 5-week CBDL rats with or without pifithrin-μ, or GW4869 administration. Data are presented as the mean ± SD (n = 5). *p < 0.05, compared with the sham-operated group; ^#p < 0.05 compared with CBDL group