Extended Data Fig. 2: AGER1 induction or RAGE deletion in hepatocytes reverses fast stress relaxation, and the appearance of transformed foci.
From: Matrix viscoelasticity promotes liver cancer progression in the pre-cirrhotic liver
a-b. Additional data of NASH-related HCC model combined with AAV8-mediated AGER1 induction. Representative stress relaxation curves (a) with or without AGER1 induction. H&E images (b), corresponding to the GS/myc-tag images in the main Fig. 2o. Scale bar, 300 μm. c-j. Additional data of the NASH-related HCC model in the hepatocyte-specific RAGE deleted (RAGEHepKO) mice. Schematics of the HDI using hMet/SB transposase with wild-type (control) or mutant β-catenin in RAGEHepKO or fl/fl mice (c). d. H&E and GS/myc immunohistochemistry were performed on sequential slides, circles represent foci, arrows indicate transduced cells. Scale bar, 300 μm. e. Quantification of foci (n = 5 each, 20 areas/per mouse). f. Liver AGEs were lower in RAGEHepKO in mice (n = 5 each). Rheometry studies, g-j. Liver stiffness (g) and viscoelasticity (h-j) were assessed (τ1/2 represents timescales at which the stress is relaxed to half its original value; increase in τ1/2 denotes lower viscoelasticity, j). There was no significant difference in stiffness, but improved viscoelasticity in RAGEHepKO mice (n = 5 each). Error bars represent mean ± s.e.m. n refers to individual mice. One-way ANOVA was used followed by Tukey’s multiple comparison test.
