[Obstruction of TGF-beta1 signal transduction by anti-Smad4 gene can therapy experimental liver fibrosis in the rat].
OBJECTIVE
To study the therapeutic effects to block the TGF-beta1 (transforming growth factor beta1) signal transduction by antisense Smad4 gene on experimental fibrotic liver.


METHODS
Using the rat model of liver fibrosis induced by Carbon Tetrachloride (CCl4)/ethanol, we transfected antisense Smad4 gene mediated by adenovirus via portal vein infusion into the liver, and observed the expression of Smad4 by Retro-Polymerase Chain Reaction (RT-PCR) and Western Blot. We also investigated the pathologic features and collagen expression.


RESULTS
In the non-therapeutic cirrhotic liver, the expression of Smad4 mRNA was significantly increased than normal liver, and so was the collagen I. After antisense Smad4 gene being transfected, the expression of Smad4 mRNA and that of collagen I in the therapeutic liver was significantly decreased, compared with the non-therapeutic cirrhotic liver. The fibrous degree of therapeutic liver was also reduced compared with the non-therapeutic fibrous liver.


CONCLUSIONS
These results indicate that because antisense Smad4 gene could block TGF-beta1 signal transduction by reducing the expression of Smad4, so it could inhibit the production of extracellular matrix (ECM) and improve hepatic fibrosis.
Xu
Xin-bao
XB
Hepatobiliary Surgery Department, People's Hospital, Beijing University, Beijing 100044, China.
He
Zhen-ping
ZP
Liang
Zhi-qing
ZQ
Leng
Xi-sheng
XS
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016375:Antisense Elements (Genetics) / Q000627:therapeutic use*; D024042:Collagen Type I / Q000032:analysis; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D051901:Smad4 Protein; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D053773:Transforming Growth Factor beta1
D016375:Antisense Elements (Genetics); D024042:Collagen Type I; D004268:DNA-Binding Proteins; D051901:Smad4 Protein; C490811:Smad4 protein, rat; C508962:Tgfb1 protein, rat; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1