Effects of Smad4 on liver fibrosis and hepatocarcinogenesis in mice treated with CCl4/ethanol.
10.3760/cma.j.issn.1007-3418.2010.02.010
- Author:
Xin-bao XU
1
;
Zhen-ping HE
;
Xi-sheng LENG
;
Zhi-qing LIANG
;
Ji-run PENG
;
Hong-yi ZHANG
;
Hong-yi ZHANG
;
Mei XIAO
;
Hui ZHANG
;
Cheng-li LIU
;
Xi-dong ZHANG
Author Information
1. Hepatobiliary Surgery Department, Airforce General Hospital of the PLA, Beijing 100142, China. xu_xinbao@sohu.com
- Publication Type:Journal Article
- MeSH:
Animals;
Carbon Tetrachloride;
administration & dosage;
Disease Models, Animal;
Ethanol;
administration & dosage;
Female;
Liver Cirrhosis, Experimental;
chemically induced;
metabolism;
pathology;
Liver Neoplasms, Experimental;
chemically induced;
metabolism;
pathology;
Male;
Mice;
Mice, Knockout;
RNA, Messenger;
genetics;
metabolism;
Reverse Transcriptase Polymerase Chain Reaction;
Signal Transduction;
Smad Proteins;
genetics;
metabolism;
Smad4 Protein;
genetics;
metabolism;
Tissue Inhibitor of Metalloproteinase-1;
genetics;
metabolism;
Transforming Growth Factor beta1;
genetics;
metabolism
- From:
Chinese Journal of Hepatology
2010;18(2):119-123
- CountryChina
- Language:Chinese
-
Abstract:
To study the effects of Smad4 on liver fibrosis and hepatocarcinogenesis in mice treated with CCl(4)/ethanol. The wild-type mice (Smad4 +/+) and the Smad4 knockout mice (Smad4 +/-) were injected subcutaneously with carbon tetrachloride(CCl(4))/ethanol twice a week for twenty weeks. The expression of Smad4, TGFbeta1, Smad2, Smad3, Smad6, TIMP1, MMP2 and MMP9 was detected by RT-PCR. In the cirrhotic liver, the expression of Smad4 mRNA was significantly higher than that in the normal liver. Comparing with wild-type mice (Smad4 +/+), the TGFbeta1-Smad4 signaling was markedly attenuated in the Smad4 knockout mice (Smad4 +/-). After induction by CCl(4)/ethanol, the hepatic fibrosis in the Smad4 knockout mice (Smad4 +/-) was obviously alleviated compared with the wild-type mice (Smad4 +/+), and the incidence rate of hepatocarcinogenesis of the former was also lower than that of the latter(32.0% vs 41.9%). These results indicate that knocking out Smad4 can delay the progression of liver fibrosis and liver cancer.
