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 7

HIF-1α-mediated response. (a) IHC staining of liver tissue of wild-type mice treated with atherogenic diet constituents performed with anti-HIF-1α marker. (1) Control group: mild DAB staining of HSCs in extrahepatocyte area. (2) CHOL group and (3) CA group: prominent DAB staining of HSC aggregation areas. (4) CHOL+CA group: multiple clusters of hepatocyte-expressing HIF-1α marked with intense DAB staining. . (b) HIF-1α nuclear protein levels in hepatocytes of wild-type mice treated with atherogenic diet constituents. (c) HIF-1α downstream activity in hepatocytes of wild-type mice represented by Glut-1 and HO-1 relative mRNA levels. All values are expressed as (). (d) IHC staining of liver tissue of Mdr2-/- mice performed with an anti-HIF-1α marker: (1) Mdr2-/- Control group: multiple brown-colored areas (DAB stained) of hepatic stellate cells (HSC) with elevated HIF-1α expression. (2) Mdr2-/- CHOL group: mild brown staining (DAB staining) of hepatic stellate cells (HSC). . (e) HIF-1α nuclear protein levels in hepatocytes of Mdr2-/- mice. (f) HIF-1α downstream activity in hepatocytes of Mdr2-/- mice represented by Glut-1 and HO-1 relative mRNA levels. All values are expressed as (). Means with different letters are statistically different, .

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