[Changes in TGF-beta1/Smads signaling pathway in rats with chemical hepatocarcinogenesis].
OBJECTIVE
To investigate the changes in transforming growth factor beta 1 (TGF-beta1)/Smads signaling pathway in rats with chemical hepatocarcinogenesis.


METHODS
Fresh diethylnitrosamine (DENA) solution was administered in SD rats to induce hepatocellular carcinoma (HCC). The protein expressions of TGF-beta1, phosphorylated Smad2, Smad4 and Smad7 were detected in these rats with immunohistochemistry, and the mRNA expression of Smad4 was evaluated with RT-PCR.


RESULTS
Cirrhotic nodules occurred in the rats 8 weeks after DENA treatment, and HCC nodules were found 16 weeks after the treatment. In the normal liver tissue, very low levels of TGF-beta1 and Smad4 expressions, low Smad7 expression and high phosphorylated Smad2 expression were detected. The development of liver cirrhosis was accompanied by increased expressions of TGF-beta1, Smad4 and Smad7 but at 8 weeks after DENA treatment, the expression of phosphorylated Smad2 was significantly decreased, followed then by gradual increment till nearly the normal level. Twenty-two weeks after DENA treatment, Smad4 expression in liver tissue decreased markedly as compared with the levels at 8 and 16 weeks. The expressions of Smad4 and phosphorylated Smad2 in the HCC tissue was significantly lower than those in normal liver tissue.


CONCLUSIONS
Hepatocarcinogenesis involves very complex mechanisms, can can be related partially to the decreased Smad4 and phosphorylated Smad2 expression and TGFbeta1 and Smad7 overexpression in advanced stage of liver cirrhosis.
Hua
Yun-peng
YP
Department of Hepatobiliary Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China. hyp0427@163.com
Li
Shao-qiang
SQ
Lai
Jia-ming
JM
Liang
Li-jian
LJ
Peng
Bao-gang
BG
Liang
Hui-zhen
HZ
Huang
Jie-fu
JF
D000818:Animals; D004052:Diethylnitrosamine; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism*; D051906:Smad7 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051901:Smad4 Protein; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1; D004052:Diethylnitrosamine