Fig. 1: Hepatic PHGDH deficiency exacerbates oxidative stress-associated acute or chronic liver injury.

a c57BL/6J mice were intraperitoneally injected with 250 mg/kg APAP. Livers were collected at 0 h, 8 h or 16 h after APAP treatment (n = 3 in each time point). Immunoblotting analysis was performed and shown on the left panel. The statistical analysis of relative protein levels was shown on the right panel. IB, immunoblotting. b c57BL/6 J mice were intraperitoneally injected with 250 mg/kg APAP. Livers were collected at 0 h or 16 h after APAP treatment. Phgdh mRNA levels in mouse livers were examined (n = 5 in each time point). c‒e Phgdh^fl/fl and Phgdh^LKO mice were intraperitoneally injected with normal saline (control) or 250 mg/kg APAP. 24 h after treatment, serum ALT and AST levels were detected by kit (c). Liver necrosis area in H&E-stained sections were circled and quantified (d). Positive liver cells in TUNEL-stained sections were quantified (e). Representative images of H&E staining or TUNEL staining were shown on the left panel and statistical analysis were shown on the right panel (n = 5 per group). f Survival of Phgdh^fl/fl and Phgdh^LKO mice intraperitoneally injected with normal saline (control) or 750 mg/kg APAP during 72 h (n = 13 per group). g‒i Phgdh^fl/fl and Phgdh^LKO mice were fed with irradiated diet with or without 0.1% DDC for 2 weeks. Serum ALT and AST levels were detected in these mice (g). Mouse livers were dissected and subjected to Sirius Red staining (h) and TUNEL staining (i) (n = 6 per group). Survival data are based on Long-rank test (f). Other data are means ± SD. Each point represents an individual mouse. P values were determined by two-tailed Student’s t-test.