Fig. 5: DDC-diet-induced ductular reaction in Tjp2 cKO mice requires Yap/Taz.

a, b Western blot analysis and quantification of Yap, Taz and pSer127 Yap expression in isolated hepatocytes from control and Tjp2 cKO mice fed normal chow. c Immunohistochemistry staining for Yap in control and Tjp2 icKOHC liver sections after a 28-day DDC-diet. Scale bar: 50 μm. d, f Immunofluorescence labeling of active (e.g. not S127 phosphorylated) Yap and HNF4α, a nuclear hepatocyte marker in liver sections of mice fed a standard (d) or a DDC- supplemented (f) diet. Scale bar: 20 μm. e, g Quantification of Yap and HNF4α-positive nuclei. h Relative mRNA expression levels of key Hippo effectors and target genes in liver of control or Tjp2 cKO mice fed normal or DDC-supplemented chow. i Western blot analysis of Yap and Wwtr1/Taz to verify their deletion in the liver of the corresponding mouse lines. j Liver to body weight ratios for the indicated mouse lines fed DDC diet for a 28-day period. k H&E staining of liver sections for the indicated mouse lines after a 28-day DDC-diet. Scale bar: 100 μm. l, m Immunohistochemistry staining for Ck19 in liver sections for the indicated mouse lines after a 28-day DDC diet and quantification of the Ck19-positive area. Scale bar: 100 μm. Data in (b, e, g, h, j, m) shown as mean ± SD, unpaired Student’s t test. *p < 0.05; **p < 0.005, ***p < 0.0005, ns=not significant (p > 0.05), with p < 0.05 considered a significant difference. (b): n = 3 or 4, (e) and (g): n = 10, (h): n = 3, (j): n = 7, (m): n = 6 mice per cohort. icKOHH, tamoxifen-induced hepatocyte deletion.