Fig. 4

Knockout of Sct ameliorates DR and senescence in EtOH-fed mice. A There was a significant increase in DR in EtOH-fed WT mice compared to CD-fed WT mice, which was significantly decreased in EtOH-fed Sct^−/− mice compared to EtOH-fed WT mice. Data are mean ± SEM of 5 experiments from CD-fed WT mice (n = 6), WT fed-EtOH mice (n = 5), CD-fed Sct^−/− mice (n = 4) and EtOH-fed Sct^−/− mice (n = 3), Orig. magn., 20X, scale bar: 100 μm. *p < 0.05 vs. CD-fed WT mice; ^#p < 0.05 vs. EtOH-fed WT mice. Red arrows indicate the bile ducts positive for CK19. B–C Measurement of cellular senescence in liver sections by [B] SA-β-gal staining (Orig. magn., 20X, scale bar: 100 μm) and C immunofluorescence for p16 in liver sections (co-stained with CK19 or HNF4α, respectively). Orig. magn., 20X, scale bar: 100 μm; Black arrows indicate senescent bile ducts, whereas white arrows indicate p16 positivity of cholangiocytes or hepatocytes. D By SA-β-Gal there was enhanced biliary senescence in liver sections from patients with alcoholic cirrhosis (n = 4) compared to human healthy controls (n = 3); orig. magn 20X, scale bar: 100 μm. Data are mean ± SEM of 5 random fields *p < 0.05 vs. healthy controls. Representative images in liver sections from patients with alcoholic cirrhosis (n = 3) and healthy controls (n = 3). Black arrows indicate senescent bile ducts. E By qPCR, there enhanced mRNA expression of p18 in total liver samples from patients with alcoholic cirrhosis (n = 16) compared to healthy controls (n = 10). Data are mean ± SEM of two experiments for each sample. *p < 0.05 vs healthy controls