[Salianic-acid B inhibits MAPK signaling in activated rat hepatic stellate cells].
OBJECTIVE
To investigate the inhibiting effect of salianic-acid B (SA-B) on mitogen-activated protein kinase (MAPK) Signaling in activated rat hepatic stellate cells (HSCs).


METHODS
HSCs were isolated from normal rat by in situ perfusion and Nycodenz density-gradient centrifugation method. HSCs were primarily cultured on uncoated plastic for 7 days. Then cells were stimulated with 10ng/ml transforming growth factor-beta1 (TGF-beta1) after incubated with 10-6 M/L SA-B. The effects of SA-B on Extracellular-regulated kinase (ERK) expression and its phosphorylation. Transforming growth factor beta1 receptor I (TbetaR I) and transforming growth factor beta1 receptor II (TbetaR II) on HSCs, type I collagen expression in HSC Induced by TGF-beta1 were detected with western blot assay. Quantity of Type I collagen in the medium of HSCs was detected by ELISA. Matrix metalloproteinase 2, 9, 13 (MMP-2, MMP-9 and MMP-13) in the medium of HSCs was tested by Zymography.


RESULTS
The phosphorylation of ERK1/2 in HSCs with or without TGF-beta1 was inhibited by SA-B. The expression of TbetaR I and TbetaR II on HSCs can not be affected by SA-B. The synthesization of Type I collagen in HSCs was decreased by SA-B; The synthesization and secretion of type I collagen in HSCs with TGF-beta1 were reduced by SA-B too. SA-B had no effect on the activity of MMP-2 and MMP-13, but induced the activity of MMP-13.


CONCLUSIONS
SA-B inhibits ERK signaling induced by TGF-b1 in HSC. This inhibition has no association with the expression of TbetaR I and TbetaR II on HSCs. SA-B reduces the synthesization and secretion of Type I collagen in HSC by means of inhibiting TGF-beta1 signaling, which might be not related to the degrading activities of MMPs.
Xue
Dong-ying
DY
Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Hong
Jia-he
JH
Xu
Lie-ming
LM
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053630:Depsides
D001572:Benzofurans; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D016212:Transforming Growth Factor beta; C076944:salvianolic acid B; D053630:Depsides