Figure 1.
Loss of Tet2 in myeloid cells exacerbates liver fibrosis. (A) Representative pictures of fibrotic liver from three types of Tet2-deficient mice treated with olive oil or CCl4. Sys, systemic Tet2 KO; Mye: myeloid cell–specific Tet2 KO; Alb: hepatocyte-specific Tet2 KO. 7-wk-old Tet2-deficient and Tet2-WT littermates were used to establish liver fibrosis model (n = 5 for each group). Pathological liver fibrosis lesions are indicated by green arrows in the Tet2ΔSys and Tet2ΔMye groups. Scale bar, 5 mm. (B) Statistical analysis of liver/body weight ratios of each group as shown in Fig. 1 A (n = 5 for each group). (C–F) mRNA levels of Acta2 (C), Col1a1 (D), Pdgfr (E), and Timp1 (F) in liver tissues of mice depicted in Fig. 1 A (n = 5 for each group). Gene expression levels were normalized to Gapdh. (G) Protein levels of collagen I and α-SMA in the liver tissues of different groups of mice were quantified by western blotting assay. Protein expression levels were normalized to Lamin B. (H and I) The Picrosirius red staining (scale bar, 125 μm) (H) and statistical analysis (I) of ratio of positive staining area (n = 4 for each group). Statistical analysis was performed using Image-Pro Plus 6.0. (J–L) IHC staining (scale bar, 100 μm) (J) and statistical analysis of α-SMA (K) and collagen I (L) of ratio of positive staining area of liver tissues to analyze collagen deposition and expression in different groups of mice. Statistical analysis was performed using Image-Pro Plus 6.0 (n = 4 for each group). (M and N) Serum levels of Col IV (M) and HA (N) in different types of Tet2-deficient mice with liver fibrosis (n = 5 for each group). Data are representative of at least two independent experiments with similar results (A–N). All data are shown as mean ± SD and were analyzed by two-way ANOVA with Tukey’s multiple comparison test (B–F, I, and K–N). ***P < 0.001; **P < 0.01; *P < 0.05; P > 0.05 not significant (ns). Timp1, TIMP metallopeptidase inhibitor 1; Pdgfr, platelet-derived growth factor receptor. Source data are available for this figure: SourceData F1.

Loss of Tet2 in myeloid cells exacerbates liver fibrosis. (A) Representative pictures of fibrotic liver from three types of Tet2-deficient mice treated with olive oil or CCl4. Sys, systemic Tet2 KO; Mye: myeloid cell–specific Tet2 KO; Alb: hepatocyte-specific Tet2 KO. 7-wk-old Tet2-deficient and Tet2-WT littermates were used to establish liver fibrosis model (n = 5 for each group). Pathological liver fibrosis lesions are indicated by green arrows in the Tet2ΔSys and Tet2ΔMye groups. Scale bar, 5 mm. (B) Statistical analysis of liver/body weight ratios of each group as shown in Fig. 1 A (n = 5 for each group). (C–F) mRNA levels of Acta2 (C), Col1a1 (D), Pdgfr (E), and Timp1 (F) in liver tissues of mice depicted in Fig. 1 A (n = 5 for each group). Gene expression levels were normalized to Gapdh. (G) Protein levels of collagen I and α-SMA in the liver tissues of different groups of mice were quantified by western blotting assay. Protein expression levels were normalized to Lamin B. (H and I) The Picrosirius red staining (scale bar, 125 μm) (H) and statistical analysis (I) of ratio of positive staining area (n = 4 for each group). Statistical analysis was performed using Image-Pro Plus 6.0. (J–L) IHC staining (scale bar, 100 μm) (J) and statistical analysis of α-SMA (K) and collagen I (L) of ratio of positive staining area of liver tissues to analyze collagen deposition and expression in different groups of mice. Statistical analysis was performed using Image-Pro Plus 6.0 (n = 4 for each group). (M and N) Serum levels of Col IV (M) and HA (N) in different types of Tet2-deficient mice with liver fibrosis (n = 5 for each group). Data are representative of at least two independent experiments with similar results (A–N). All data are shown as mean ± SD and were analyzed by two-way ANOVA with Tukey’s multiple comparison test (B–F, I, and K–N). ***P < 0.001; **P < 0.01; *P < 0.05; P > 0.05 not significant (ns). Timp1, TIMP metallopeptidase inhibitor 1; Pdgfr, platelet-derived growth factor receptor. Source data are available for this figure: SourceData F1.

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