PPARα activation promotes proliferation of Sox9+ hepatocytes, and FXR suppresses proliferation of Sox9+ hepatocytes after CCl4-induced chronic liver injury in Sox9-CreERT2; Rosa26-mTmG mice
(A) Schematic diagram showing mTom/mGFP reporter gene expression in the absence and presence of tamoxifen (TAM)-inducible Cre-mediated recombination.
(B) Sox9-CreERT2; Rosa26-mTmG mice were intraperitoneally injected with a single dose of tamoxifen once per day for three days before treatment. The Sox9-CreERT2; Rosa26-mTmG mice were received intraperitoneal paraffin oil injection (control group) or CCl4 injection twice per week for four weeks and these mice were orally gavaged with either Veh, GW7647, or GW4064 four times a week for four weeks. BrdU was injected twice per day for two days before sacrifice.
(C) GFP(Sox9)/Hnf4α double staining was performed. Graphs show percentages of GFP+Hnf4α+ cell (n = 5). Scale bar represents 20μm.
(D) GFP(Sox9)/BrdU double staining was performed. Arrowheads depict the asymmetric division. Graphs show percentages of GFP+BrdU+ cell (n = 5). Scale bar represents 20μm. Data are expressed as means ± SD. Comparisons between multiple groups were performed using ordinary one-way ANOVA with the Dunnett's multiple comparison test. Significant difference is presented at the levels of ∗p < 0.05 and ∗∗p < 0.01.