title: Effect of S-adenosyl-L-methionine on the activation, proliferation and contraction of hepatic stellate cells.
abstract: 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.
authors.affiliation: Department of Anatomy, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Matsui
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
mesh_terms: 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*
chemical_list: D000199:Actins; D024042:Collagen Type I; D019332:Endothelin-1; D020574:Proto-Oncogene Proteins c-sis; D012436:S-Adenosylmethionine