Cholesterol Induces Nrf-2- and HIF-1α-Dependent Hepatocyte Proliferation and Liver Regeneration to Ameliorate Bile Acid Toxicity in Mouse Models of NASH and Fibrosis

Figure 6

Proliferative effects of cholesterol in liver tissue. (a) IHC staining of liver tissue of wild-type mice supplemented with atherogenic diet constituents performed with PCNA staining: (1) Control group: no PCNA-positive nuclei. (2) CHOL group: no PCNA-positive nuclei. (3) CA group: no PCNA-positive nuclei. (4) CHOL+CA group: multiple brown-colored nuclei, stained with DAB, are nuclei of cells undergoing proliferative stage. . (b) PCNA relative protein levels in wild-type mice treated with atherogenic diet components. All values are expressed as (). (c) IHC staining of liver tissue of Mdr2-/- mice performed with an anti-PCNA marker: (1) Mdr2-/- Control group: multiple brown-colored nuclei (DAB stained) of cells undergoing proliferative stage. (2) Mdr2-/- CHOL group: major brown staining (DAB staining) of multiple cell nuclei undergoing proliferative stage. . (d) PCNA relative protein levels in Mdr2-/- mice. (e) Hepatic growth factor levels (HGF) in Mdr2-/- mice. All values are expressed as (). Means with different letters are statistically different, . (f) Increased phosphorylation of Akt and Erk proteins in Mdr2-/- mice treated with cholesterol for 6 weeks (), .

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