[Effects of Erk signal transduction on the cell cycle of rat hepatic stellate cells stimulated by acetaldehyde].
OBJECTIVE
To investigate the effect of PD98059 on the proliferation and cell cycle of rat hepatic stellate cells (HSCs) stimulated by acetaldehyde and explore its mechanism.


METHODS
Rat HSCs stimulated by acetaldehyde were incubated with different concentrations of PD98059. Cell proliferation was assessed by MTT colorimetric assay. Cell cycle was analysed by flow cytometry. The mRNA of cyclin D1 and CDK4 were examined by RT-PCR.


RESULTS
20, 50, 100 micromol/L PD98059 could significantly inhibit the proliferation of HSCs stimulated by acetaldehyde in a does-dependent manner (0.109+/-0.020, 0.081+/-0.010 and 0.056+/-0.020 vs 0.146+/-0.030, F=31.385, P<0.05) and provoke G0/G1 phase arrest of HSCs stimulated by acetaldehyde in a does-dependent manner (61.9%+/-6.3%, 64.1%+/-3.3% and 70.9%+/-4.8% vs 55.2%+/-4.4%, F=16.402, P<0.05). 50, 100 micromol/L PD98059 could markedly inhibit cyclin D1 mRNA expression of HSC stimulated by acetaldehyde (0.56+/-0.04 and 0.46+/-0.03 vs 0.65+/-0.07, F=68.758, P<0.05) and CDK4 mRNA expression (0.39+/-0.07 and 0.33+/-0.05 vs 0.50+/-0.06, F=29.406, P<0.05).


CONCLUSIONS
The Erk signal transduction pathway plays an important role in regulating the proliferation and cell cycle of rat hepatic stellate cells stimulated by acetaldehyde, which may be partly related to its regulative effect on the expression of cyclin D1 gene and CDK4 gene
Jiang
Ming-de
MD
Department of Gastroenterology, General Hospital of Chengdu Military Region, Chengdu 610083, China.
Ma
Hong-de
HD
Zhong
Xian-fei
XF
Xie
Fang-wei
FW
Zeng
Wei-zheng
WZ
D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects*; D011518:Proto-Oncogene Proteins; D051381:Rats
D004791:Enzyme Inhibitors; D005419:Flavonoids; D011518:Proto-Oncogene Proteins; D019938:Cyclin D1; C495903:Cdk4 protein, rat; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D000079:Acetaldehyde; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one