Abnormal expression of Smurf2 during the process of rat liver fibrosis.
OBJECTIVE
Liver fibrosis is a prelude of liver cirrhosis. Currently the molecular mechanism of liver fibrosis is not clear. The purpose of this study is to screen the abnormally expressed genes of liver fibrosis and to illustrate the changes of Smurf2 expression in the process of liver fibrosis.


METHODS
A liver fibrosis model was established in rats by injection of tetrachlormethane (CCl(4)). A cDNA microarray analysis was performed on the liver at mid-stage of fibrosis. Thereafter, a semi-quantitative RT-PCR, Western blot analysis and immunohistochemistry test were performed for determining Smurf2, Smad2 and SnoN at week 1, 2, 4 and 8 of establishing the liver fibrosis model.


RESULTS
Smurf2, FGG, PTAFR, CYP2D6, among others, increased in the fibrosis liver and a semi-quantitative RT-PCR confirmed the reliability of the cDNA microarray analysis. Smurf2 in the liver fibrosis model group was at the same level as that of control group at week 1, but decreased at week 2 and 8 and increased at the week 4. Smad2 increased at week 2 and 8 but increased at week 4. However, Smad2 mRNA increased to the same level at week 4 as that at week 2 and 8. The decrease of Smad2 at week 4 may be due to the enhancement of ubiquitination and proteolytic degradation of Smad2 by the increase of Smurf2. SnoN decreased at week 4 and 8 because of the ubiquitination and degradation caused by Smurf2. The decrease of SnoN may explain the progress of liver fibrosis in spite of the decrease of Smad2 at week 4.


CONCLUSIONS
This study screened the abnormally expressed genes of liver fibrosis and illustrated the changes of Smurf2, Smad2 and SnoN during the process of liver fibrosis.
Cai
Yu
Y
Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Shen
Xi Zhong
XZ
Zhou
Chao Hui
CH
Wang
Ji Yao
JY
D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
D009419:Nerve Tissue Proteins; C511209:Skil_v1 protein, rat; D051899:Smad2 Protein; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases