Effect of S-adenosyl-L-methionine on the activation, proliferation and contraction of hepatic stellate cells.
Inhibition of hepatic stellate cell activation is an important clinical aspect for the control of liver inflammation, fibrosis and cirrhosis. S-adenosyl-L-methionine (SAM), an intermediate product of L-methionine metabolism, is a precursor of glutathione and an endogenous methyl donor. Although the hepato-protective action of SAM has been reported in several animal models, the effect of SAM on the function of hepatic stellate cells has not been elucidated. Using a primary-culture model of hepatic stellate cells, we found that SAM blunts the activation process as indicated by the suppression of expression of collagen alpha1(I) and smooth muscle alpha-actin. SAM also hampers the DNA synthesis of hepatic stellate cells stimulated with a dimer of platelet-derived growth factor-B via the inhibition of phosphorylation of PDGF receptor-beta and down-stream signaling pathways. SAM additionally inhibits the contraction of hepatic stellate cells by disturbing the formation of F-actin stress fibers and phosphorylated myosin light chains. Thus, SAM regulates the activation of hepatic stellate cells and may clinically contribute to therapy targeted at human liver fibrosis.
Matsui
Hiroko
H
Department of Anatomy, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Kawada
Norifumi
N
D000199:Actins / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D019332:Endothelin-1 / Q000187:drug effects* / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012436:S-Adenosylmethionine / Q000378:metabolism / Q000494:pharmacology*
D000199:Actins; D024042:Collagen Type I; D019332:Endothelin-1; D020574:Proto-Oncogene Proteins c-sis; D012436:S-Adenosylmethionine