Fig. 2: GSDMD deficiency ameliorates acute liver injury and chronic fibrosis in RILD.

A Representative high magnification images of Hematoxylin Eosin staining (HE) staining in Gsdmd^FL/FL and Gsdmd^∆Hep mice (n = 5/group) treated with or without one single 30 Gy hepatic radiation. (Scale bars, 200×, 200 μm, 400×, 50 μm). B-D Representative liver macroscopic image (B), ɑ-SMA staining (C) and sirius-red staining (D) in Gsdmd^FL/FL or Gsdmd^∆Hep mice in LT-RILD. Scale bars, 400×, 50 μm; 200×, 100 μm. Statistical analysis of ɑ-SMA and collagen area were present in the right, 5 fields were observed per mice (n = 5/group). Gsdmd^FL/FL-IR vs Gsdmd^∆Hep-IR: ɑ-SMA, ***p = 0.0001; collagen area, ***p = 0.0004. E Immunoblot analysis of liver protein expression of COL1A1, Fibronectin and ɑ-SMA from Gsdmd^FL/FL and Gsdmd^∆Hep mice (n = 1, no IR; n = 3, Gsdmd^FL/FL-IR; n = 5, Gsdmd^∆Hep-IR). F Key hepatic profibrogenic genes of Col1a1, Tgfb1 and Timp1 in Gsdmd^FL/FL and Gsdmd^∆Hep mice treated with IR (n = 3/group, Ctrl; n = 5/group, LT). Gsdmd^FL/FL-IR vs Gsdmd^∆Hep-IR: Col1a1, p = 0.0008; Tgfb1, p = 0.0003; Timp1, p = 0.0003. G Serum levels of liver function markers ALT, AST and ALB were determined in Ctrl-, ST- and LT-RILD groups (n = 3/group, Ctrl; n = 5/group, ST/LT). ST-Gsdmd^FL/FL vs Gsdmd^∆Hep: ALT, p = 2.087E-06; AST, p = 6.926E-05; ALB, p = 0.002. LT-Gsdmd^FL/FL vs Gsdmd^∆Hep: ALT, p = 1.857E-05; AST, p = 4.838E-05; ALB, p = 1.273E-05. H Supernatant levels of liver function markers ALT, AST and ALB were determined in hepatocytes with and without IR treatment (Each sample was from 3 biologically independent replicates). ALT, p = 1.156E-06; AST, p = 2.89E-07; ALB, p = 0.002. Data are expressed as mean ± SEM. p values were calculated using two-way ANOVA with Fisher’s LSD multiple comparisions test (C, D, F–H). No data were excluded from the analyses. Source data are provided as a Source Data file.