Obstruction of TGF-beta1 signal transduction by anti-Smad4 gene can therapy experimental liver fibrosis in the rat.
- Author:
Xin-bao XU
1
;
Zhen-ping HE
;
Zhi-qing LIANG
;
Xi-sheng LENG
Author Information
- Publication Type:Journal Article
- MeSH: Adenoviridae; genetics; Animals; Antisense Elements (Genetics); therapeutic use; Collagen Type I; analysis; DNA-Binding Proteins; antagonists & inhibitors; genetics; Liver; pathology; Liver Cirrhosis, Experimental; metabolism; pathology; therapy; Male; Rats; Rats, Wistar; Signal Transduction; Smad4 Protein; Trans-Activators; antagonists & inhibitors; genetics; Transforming Growth Factor beta; antagonists & inhibitors; Transforming Growth Factor beta1
- From: Chinese Journal of Hepatology 2004;12(5):263-266
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the therapeutic effects to block the TGF-beta1 (transforming growth factor beta1) signal transduction by antisense Smad4 gene on experimental fibrotic liver.
METHODSUsing 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.
RESULTSIn 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.
CONCLUSIONThese 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.
