Fig. 4: YAP activation reversely correlates with hepatic Fxr activity in both mice and humans.
a–c qPCR analysis of Bsep and Shp expression (a) in the indicated liver samples, ***P = 0.0002, ***P = 0.0003 in sequence; (b) in the indicated mouse MHOs, ****P < 0.0001; (c) in MHOs were treated with 5 µM Fxr agonist GW4064 or OCA for 48 h, ****P < 0.0001. d Total BA concentration in the medium of MHOs, ****P < 0.0001, ***P = 0.0002. e, f Gene-set enrichment analyses (GSEA) for Fxr target gene expression by comparing TetO-YAP MHOs with and without Dox treatment (e), and control with YAP knockout MHOs (f). g qPCR analysis for BSEP and SHP expression in the human MHOs. Cells were treated for 48 h, with 3 µM TDI-011536 (TDI) to activate YAP, 5 µM GW4064 to activate FXR, and 0.5 µM Verteporfin (VP) to inhibit YAP-TEAD binding, **P = 0.0016 (BSEP), ***P = 0.0003 (SHP), ****P < 0.0001. h Total BA concentration in the medium of human MHOs with the indicated treatment, ****P < 0.0001, **P = 0.0028, ***P = 0.0003. i The predictions for HCC samples with ‘liver tumor YAP signature’ (red and blue) and ‘Hepatic FXR signature’ (orange and green) in LIRI-JP cohort (n = 236). Heatmap shows the expression of listed genes, r values determined by Pearson correlation comparing YAP activity with gene expression. j Expression of selected genes in YAP ‘high’ or ‘low’ groups of HCC samples from the cohort, n = 31 in YAP ‘high’ group, n = 68 in YAP ‘low’ group, box extends from the 25th to 75th percentiles, line in the middle of the box is plotted at the median, whiskers down to the minimum and up to the maximum value, and p-values were determined by two-sided unpaired t-test with Welch’s correction, ***P = 0.0001, *P = 0.026, ****P < 0.0001. k, l GSEA for Fxr target gene expression by comparing YAPHigh HCC samples with all non-tumor samples (k), YAPlow HCC with all non-tumor samples in the cohort (l). n = 4 independent experiments (a), n = 3 independent experiments (b−d, g, h), n = 3 biological replicates (e, f). Data are presented as Mean ± SD, p-values were determined by two-sided unpaired t-test (a). Data are presented as Mean ± SD, p-values were determined by 1-way ANOVA with Sidak’s test (b–d, g, h). Source data are provided as a Source Data file.
