Figure 6.

VEGF and CXCL9 modulation in resolution after CCl4-induced injury. C57BL/6 mice were treated with CCl4 for 4 weeks. One day after the final dose of CCl4, mice were administered anti-VEGF or control antibody (50 μg per injection, IP ×2/week). Mice were sacrificed 4 weeks after discontinuation of CCl4. Fibrosis resolution was attenuated by anti-VEGF assessed by Sirius Red staining (A) (n = 10, *P < .05). Mice received adenovirus-expressing mouse VEGF (AdVEGF) (0.8 × 10⁹ PFU/kg) or LacZ through tail vein injection. Mice were sacrificed at 2 weeks after final dose of CCl4. Fibrosis was assessed using Sirius Red stain (B). VEGF overexpression was associated with enhanced fibrosis resolution (n = 10; *P < .05). Total liver mRNA was subjected to real-time polymerase chain reaction analysis to evaluate VEGF, CSF1r, NCF1, CXCL9, and MMP13 mRNA levels (C). C57BL/6 mice were treated with CCl4 for 6 weeks. One day after the final CCl4 dose, mice were injected with AdCXCL9 or AdLacZ (single dose 4 × 10¹⁰ PFU/kg through tail vein). Mice were sacrificed 1 week after discontinuation of CCl4. Total liver mRNA was subjected to real-time polymerase chain reaction analysis to evaluate CXCL9, MMP13, MMP9, and MMP2 mRNA levels (D). Liver sections were stained with Sirius Red (200×) for morphometric quantification, which showed that AdCXCL9 promotes tissue repair (E) (n = 7; *P < .05). (C, control IgG; V, anti-VEGF antibody; AdZ, AdLacZ; AdV, AdVEGF; *P < .05).