Dynamic expressions of kielin/chordin-like protein in mouse model of liver fibrosis and changes after bone morphogenetic protein-7 intervention
10.3760/cma.j.issn.1000-6680.2012.10.003
- VernacularTitle:kielin/chordin样蛋白在肝纤维化模型中的动态表达及骨形成蛋白-7干预后的表达变化
- Author:
Mei SONG
;
Yongping CHEN
;
Shaolong CHEN
;
Dazhi CHEN
;
Tao YANG
;
Zhuo LIN
- Publication Type:Journal Article
- Keywords:
Bone morphogenetic proteins;
Transforming growth factor beta 1;
RNA,messenger;
Liver cirrhosis;
Disease models,animal
- From:
Chinese Journal of Infectious Diseases
2012;30(10):587-592
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the dynamic expressions of kielin/chordin-like protein (kcp) in mouse model of hepatic fibrosis and the effects of bone morphogenetic protein-7 (BMP-7)intervention on the expressions,and to explore a new target for treatment of fibrosis.Methods A total of 50 healthy male ICR mice were divided into three groups:control group(n=10) ; model group (n=30) and BMP-7 treatment group (n=10).The model group was further divided into three subgroups according to different time points:subgroups of 4,8 and 12 weeks with 10 mice in each subgroup.The mouse model of hepatic fibrosis was established by hypodermic injection of carbon tetrachloride(CCl4 ).The mice in BMP-7 treatment group began to receive human recombmant BMP- 7via intraperitoneal injection after 8 weeks of the first administration of CC14 and lasted for 4 weeks.The serum levels of alanine aminotransferase (ALT),aspartate transaminase (AST) and albumin (Alb) were detected.The pathological changes of liver were observed under optical microscope after HE and Masson staining.The dynamic expressions of kcp mRNA and protein of each group were detected by reverse transcription-polymerase chain reaction,immunohistochemistry and Western blot.The comparison of means among groups was done by univariate ANOVA.Results In model group,ALT and AST levels increased,while Alb level gradually decreased,and peaked at week 12.BMP-7treatment could reduce the changes,and there were significant differences among groups (F=23.501,34.600 and 16.244,respectively; all P<0.05).In normal control group,the expressions of kcp mRNA and protein were low,while those in model group were gradually increased.BMP-7 treatment could achieve remission and the changes were all significantly different among groups (F=30.362 and 10.727,respectively; P<0.01 or 0.05).The expression of kcp mRNA was positively correlated with levels of transforming growth factor (TGF)-β1 mRNA and BMP-7 mRNA (r=0.760 and 0.769,respectively; both P<0.05).Conclusions BMP 7 can improve the hepatic fibrosis in mice.kcp may play an important role in the occurrence and development of liver fibrosis which is a potential therapeutic target for hepatic fibrosis.