Skip to main content
. Author manuscript; available in PMC: 2023 Apr 1.
Published in final edited form as: J Hepatol. 2021 Dec 11;76(4):910–920. doi: 10.1016/j.jhep.2021.11.031

Figure 1. Silencing hepatocyte TAZ in pre-tumor NASH mice suppresses the development of HCC tumors.

Figure 1.

(A) Livers (arrows, tumors) and liver sections of mice fed the NASH diet for 15 months. The sections were stained with H&E (imaged at 4X and 20X; bars, 1 mm and 200 μm, respectively; T, tumor) and with reticulin and ant-iglypican-3 (bars, 100 μm). (B-E) Mice were fed the NASH diet for 13 months, with AAV8-H1-shTaz (shTaz) or control vector (Scr) administered at 8 monts. (B) Experimental scheme. (C) TAZ immunoblot from non-tumor liver tissue. (D) Livers (arrows, tumors) and tumor numbers/mouse. (E) Liver sections from non-tumor areas stained for Ki67 (green) and HNF4α (red) and quantified for the percent Ki67+HNF4α+ cells (arrows, Ki67+HNF4α+ cells; bar, 100 μm). For D-E, n = 6 mice/group; means ± SEM; *p < 0.05 by Student’s t-test. (F) Livers (arrows, tumors) and liver sections of mice that were administered DMBA post-natal day 5; placed on NASH diet at 1 month of age, and analyzed at 9 months. The sections were stained with H&E, Sirius red (bars, 500 μm; T, tumor), reticulin, and anti-glypican-3 (bars, 200 μm). (G-J) Wwtr1fl/fl male mice were administered DMBA on postnatal day 5; placed on the NASH diet at 1 month; injected with AAV8-TBG-LacZ or AAV8-TBG-Cre at 5 months; and analyzed at 9 months. (G) Experimental scheme. (H) TAZ immunoblot from non-tumor liver tissue. (I) Livers (arrows, tumors) and tumor numbers and average diameter. (J) Percent Ki67+HNF4α+ cells in non-tumor areas. For I-J, n = 5 mice/group; means ± SEM; *p < 0.05 by Student’s t-test. (K) Livers (arrows, tumors) and liver sections of RosaNICD mice injected with AAV8-TBG-Cre to activate hepatocyte Notch; started on the NASH diet 1 week later; and analyed after 4 months on diet. The sections were stained with H&E, Sirius red (bars, 500 μm), reticulin, and anti-glypican-3 (bars, 200 μm). (L-O) RosaNICD or RosaNICD Wwtr1fl/fl mice were treated with AAV8-TBG-Cre; placed on NASH diet 1 week later; and analyzed 4 months later. (L) Experimental scheme. (M) TAZ immunoblot from non-tumor liver tissue. (N) Livers (arrows, tumors) and tumor numbers and average diameter. (O) Percent Ki67+HNF4α+ cells in non-tumor areas. For N-O, n = 5 mice/group; means ± SEM; *p < 0.05 by Student’s t-test.