Effects of extracellular signal-regulated kinase on rat cultured hepatic stellate cells stimulated by acetaldehyde.
OBJECTIVE
To investigate the effects of PD98059 on the cell cycle, cell proliferation, the secretion of type I collagen and expression of transforming growth factor-beta-1 mRNA in rat hepatic stellate cells stimulated by acetaldehyde.


METHODS
Rat hepatic stellate cells stimulated by acetaldehyde were incubated with different concentrations of PD98059. The cell cycle was analyzed by flow cytometry. Cell proliferation was assessed by methyl thiazolyl tetrazolium colorimetric assay. The mRNA expression of transforming growth factor-beta-1 was examined by reverse transcriptase polymerase chain reaction. Type I collagen of the culture medium was detected by enzyme-linked immunoadsorbent assay.


RESULTS
Twenty, 50 and 100 micromol/L PD98059 could significantly inhibit the proliferation and provoke a G0/G1-phase arrest of hepatic stellate cells stimulated by acetaldehyde in a dose-dependent manner. The secretion of type I collagen and transforming growth factor-beta-1 mRNA expression of acetaldehyde-induced hepatic stellate cells were markedly inhibited by 50 and 100 micromol/L PD98059, respectively.


CONCLUSIONS
Extracellular signal-regulated kinase signal transduction pathway could regulate cell proliferation, the secretion of type I collagen and transforming growth factor-beta-1 mRNA expression of rat hepatic stellate cells stimulated by acetaldehyde. This is most likely related to its regulative effect on the cell cycle.
Zheng
Shu Mei
SM
Department of Gastroenterology, General Hospital of Chengdu Military Command, Chengdu, China. zhengsm@163.com
Jiang
Ming De
MD
Zeng
Wei Zheng
WZ
Xu
Hui
H
Wang
Yun Xia
YX
Ma
Hong De
HD
Xie
Fang Wei
FW
Zhang
Yong
Y
Qin
Jian Ping
JP
Wu
Xiao Ling
XL
D000079:Acetaldehyde; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000139:chemically induced; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000187:drug effects / Q000378:metabolism
D024042:Collagen Type I; D005419:Flavonoids; D053773:Transforming Growth Factor beta1; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D000079:Acetaldehyde; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one