[Effects of Smad4 on liver fibrosis and hepatocarcinogenesis in mice treated with CCl4/ethanol].
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.
Xu
Xin-bao
XB
Hepatobiliary Surgery Department, Airforce General Hospital of the PLA, Beijing 100142, China. xu_xinbao@sohu.com
He
Zhen-ping
ZP
Leng
Xi-sheng
XS
Liang
Zhi-qing
ZQ
Peng
Ji-run
JR
Zhang
Hong-yi
HY
Zhang
Hong-yi
HY
Xiao
Mei
M
Zhang
Hui
H
Liu
Cheng-li
CL
Zhang
Xi-dong
XD
D000818:Animals; D002251:Carbon Tetrachloride / Q000008:administration & dosage; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage; D005260:Female; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D051901:Smad4 Protein / Q000235:genetics* / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D051785:Smad Proteins; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D000431:Ethanol; D002251:Carbon Tetrachloride