Extracellular histones stimulate collagen expression in vitro and promote liver fibrogenesis in a mouse model via the TLR4-MyD88 signaling pathway

Figure 1 Circulating histones are elevated in ICR mice treated with CCl₄. Typical western blots of histone H3 standard and histone H3 in plasma from mice treated with the first dose of CCl₄ (A) and CCl₄ + non-anticoagulant heparin (NAHP) (B), and a typical H3 blot before and 24 h after the last dose of CCl₄ (C); D: The mean ± SD of circulating histones at different time points, including 0 h (before the experiment), and 4, 8, 24, 48 and 84 h after first dose of CCl₄ (orange) and CCl₄ + NAHP (blue) of each week are presented. ANOVA test, ^aP < 0.05 compared to time 0; E: The mean ± SD of peak circulating histones (8 and 24 h after first CCl₄ injection of each week). ANOVA test, ^aP < 0.05 compared to time 0 (before first injection). The mean ± SE of blood alanine aminotransferase levels (F) and liver injury scores (G) from nine mice in each group following 4 wk of treatment. ANOVA test, ^aP < 0.05 compared to mice without treatment (before). ^bP < 0.05 compared to CCl₄ group. ANOVA: Analysis of variance; NAHP: Non-anticoagulant heparin; ALT: Alanine aminotransferase.