Endostar, a novel human recombinant endostatin, attenuates liver fibrosis in CCl4-induced mice

Jing Chen, Dian-Gang Liu, Guang Yang, Ling-Jian Kong, Ya-Ju Du, Hang-Yu Wang, Feng-Dong Li, Feng-Hua Pei, Ji-Tao Song, Yu-Jing Fan, Ai-Yun Liu, Xin-Hong Wang, Bao-Xin Li
Experimental Biology and Medicine 2014, 239 (8): 998-1006
Decreasing hepatic fibrosis remains one of the major therapeutic challenges in hepatology. The present study aims to evaluate the effect of Endostar on both CCl4 -induced liver fibrosis in mice and a hepatic stellate cell (HSC) line. Two main models were studied: (i) a liver fibrosis model was induced in BALB/c mice using CCl4 by intraperitoneal injection for six weeks. Six animal groups were studied: group 1: normal animals; group 2: CCl4 -induced liver fibrosis; group 3: CCl4  + Endostar 20 mg/kg/d, six weeks; group 4: CCl4  + Endostar 10 mg/kg/d, six weeks; group 5: CCl4  + Endostar 20 mg/kg/d, four weeks; group 6: CCl4  + Endostar 10 mg/kg/d, four weeks corresponded to different Endostar doses and duration of administration. Liver fibrosis was evaluated by histopathological staining and liver hydroxyproline content. Expressions of collagen type I, α-smooth muscle actin (α-SMA), TGF-β1 and VEGFR were measured by real-time polymerase chain reaction (PCR). (ii) A liver cell model. HSC-T6 cells were cultured with or without Endostar for 12 h or 24 h. Expressions of collagen type I, α-SMA, and TGF-β1 were measured by real-time PCR. Collagen I and transforming growth factor β1 (TGF-β1) contents in cell supernatant were measured by enzyme-linked immunosorbent assay. As compared to the group without Endostar, liver fibrosis scores and hydroxyproline content were decreased in both Endostar groups (P < 0.05). Moreover, Endostar inhibited the hepatic expression of α-SMA, TGF-β1, Collagen-1, VEGFR1, and VEGFR2 mRNA (P < 0.05). In the HSC-T6 cell line model, Endostar profoundly inhibited the expression of α-SMA, Collagen-1, and TGF-β1 mRNA. Expressions of Collagen-1 and TGF-β1 protein were decreased in the Endostar group as compared to the normal controls in the supernatant of HSC-T6 cells (P < 0.05). Endostar decreased both liver fibrosis in CCl4 -induced mice and collagen synthesis in HSCs in vitro. Therefore, this recombinant human endostatin is a promising compound for counteracting liver fibrosis.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"