Figure 6. Hepatic over-expression of TAp63α causes steatosis via ER stress.

(a) p63 protein levels in the liver of mice after a tail vein injection of an AAV8 over-expressing either GFP or TAp63α isoform. (b) Representative photomicrographs of hematoxylin-eosin (upper panel) and oil red O staining (lower panel) of mice liver sections (n=4 per group); (c) total liver TG content, serum AST, ALT and TG levels (n=9 AAV8-GFP and 10 AAV8-TAp63α); (d) protein levels of FAS, pJNK/JNK, pIRE/IRE, XBP1s, pPERK, peIF2α/eIF2α, cleaved caspase 3, cleaved caspase 7, ApoB100 and ApoB48; and (e) mRNA expression of CPT1, ACADM, ACADL and FATP2 in the liver of mice after hepatic over-expression of TAp63 and IP TUDCA administration (n=7 per group). (f) GRP78 protein levels in the liver of mice after a tail vein injection of an Ad over-expressing either GFP or GRP78 (n=6 per group). (g) Representative photomicrographs of hematoxylin-eosin (upper panel) and oil red O staining (lower panel) of mice liver sections (n=4 per group); (h) total liver TG content, serum AST, TG and ketone bodies levels (n=9 AAV8-GFP and 10 AAV8-TAp63α); (i) protein levels of FAS, pIRE/IRE, XBP1s, ApoB100 and ApoB48 (n=6 per group); and (j) mRNA expression of CPT1, ACADM, ACADL and FATP2 in the liver of mice after hepatic over-expression of TAp63α and Ad GRP78 administration (n=8 per group). Protein GAPDH or transferrin levels were used to normalize protein levels and control values (AAV8 GFP) were normalized to 100%. Dividing lines indicate splicings in the same gel (n=7 per group). Uncropped blots of this Figure accompanied by the location of molecular weight markers are shown in Supplementary Fig. 15 and Supplementary Fig. 16. Data are presented as mean±standard error mean (s.e.m.). Statistical significance, *P<0.05, **P<0.01 and ***P<0.001. For multiple comparison (c–e,h–j) a one way ANOVA followed by Bonferroni or Kruskal-Wallis test was performed. Student t-test was used in TAp63alpha and GRP78 liver protein levels (a,f).