Fig. 1

Notch-activated MSCs enhance the protective effects against APAP-induced hepatotoxicity. A Mice were subjected to APAP-challenged liver injury. Some mice were injected via the tail vein with human umbilical cord-derived MSCs, fibroblasts (1 × 10⁶) or PBS 24 h prior to APAP injection (400 mg/kg, i.p.). Representative histological staining (H&E) of liver tissue (n = 5 mice/group) and percent of necrotic area. Scale bars: 100 μm. B Hepatocellular function, as assessed by serum ALT levels (IU/L) (n = 5 mice/group). C Quantitative RT-PCR-assisted detection of Notch1, Notch2, Notch3, Notch4 and Cox2 expression in MSCs with or without LPS (100 ng/mL)/IFN-γ (10 ng/mL) stimulation. Representative of three experiments. D Western blot analysis of Notch2 and COX2 protein expression in MSCs with or without LPS (100 ng/mL)/IFN-γ (10 ng/mL) stimulation. (E, F) MSCs were transfected with Notch2 siRNA (siNotch2), non-specific siRNA (siNS) or COX2-siRNA (siCOX2) for 48 h. Some cells were cultured on JAG1-coated (10 μg/ml) culture plates for 24 h. E Western blot analysis of COX2 expression in MSCs. F ELISA analysis of PGE2 levels in the supernatants from MSCs. The data are means ± SD of three independent experiments. G Representative histological staining (H&E) of liver sections from MSC-siNS-, MSC-siCOX2-, MSC-siNotch2-, MSC-siNS + JAG1- or MSC-siNotch2 + JAG1-treated animals (n = 5 mice/group). Scale bars: 100 μm. H Hepatocellular function, as assessed by serum ALT levels (IU/L) (n = 5 mice/group). I Animal survival curves after a single dose of APAP (650 mg/kg, i.p.) injection over 72 h (n = 10 mice/group). All data represent the mean ± SD. *p < 0.05,**p < 0.01