Human recombinant endostatin Endostar attenuates hepatic sinusoidal endothelial cell capillarization in CCl4-induced fibrosis in mice

Abstract

The aim of the present study was to detect the effect of the recombinant human endostatin Endostar on hepatic sinusoidal capillarization in CCl4‑induced murine models of liver fibrosis. The liver fibrosis model was induced in BALB/c mice using intraperitoneal injection of CCl4 for 6 weeks. Animals were divided into the following six treatment groups: Group 1, normal animals; group 2, CCl4‑induced liver fibrosis; group 3, CCl4+Endostar 20 mg/kg/day for 6 weeks; group 4, CCl4+Endostar 10 mg/kg/day for 6 weeks; group 5, CCl4+Endostar 20 mg/kg/day for 4 weeks; and group 6, CCl4+Endostar 10 mg/kg/day for 4 weeks. The average number of fenestrae per hepatic sinusoid was determined using transmission electron microscopy. Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) 1 and 2 expression was detected by western blot analysis. There were significant differences in the number of fenestrae per sinusoid between the normal control and untreated model fibrotic mice (P<0.01), and between the untreated model and Endostar‑treated mice (P<0.05). Endostar treatment was associated with reduced levels of VEGFR1 and VEGFR2 in liver tissues (P<0.01), as well as with decreased hepatic sinusoidal endothelial cell capillarization in CCl4‑induced mouse models of liver fibrosis, and this effect may involve the VEGF pathway. However, further studies are required to confirm its involvement in other causes of liver fibrosis.

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“…Further processing included established dehydration in graded series of ethanol, embedding in epoxy resin and then cutting into ultrathin sections. Mounting of sections on copper grids was done followed by staining with uranyl acetate and lead citrate and observed under a transmission electron microscope (JEOL JEM-2100) at 100 kV 65 .…”

Molecular and tissue alterations of collagens in fibrosis

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Endostatin attenuates PDGF-BB- or TGF-&beta;1-induced HSCs activation via suppressing RhoA/ROCK1 signal pathways

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