title: Endostar, a novel human recombinant endostatin, attenuates liver fibrosis in CCl4-induced mice.
abstract: 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 CCl4by 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.
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Dian-Gang
authors.initials: DG
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, the First Hospital of Harbin, Harbin, Heilongjiang 150010, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Ling-Jian
authors.initials: LJ
authors.lastname: Kong
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Ya-Ju
authors.initials: YJ
authors.lastname: Du
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Hang-Yu
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Feng-Dong
authors.initials: FD
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Pei
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Ji-Tao
authors.initials: JT
authors.lastname: Song
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Fan
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Ai-Yun
authors.initials: AY
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Xin-Hong
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang 150086, China libaoxinyaoli@126.com.
authors.forename: Bao-Xin
authors.initials: BX
authors.lastname: Li
keywords: Carbon tetrachloride; Endostar; hepatic fibrosis; hepatic stellate cell; transforming growth factor β