Linked Life Data

15983038

Source:http://linkedlifedata.com/resource/pubmed/id/15983038

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
35
pubmed:dateCreated
2005-8-29
pubmed:abstractText
To study the anti-fibrogenic mechanisms of S-adenosylmethionine (AdoMet), transgenic mice harboring the -17 kb to +54 bp of the collagen alpha2 (I) promoter (COL1A2) cloned upstream from the beta-gal reporter gene were injected with carbon tetrachloride (CCl4) to induce fibrosis and coadministered either AdoMet or saline. Control groups received AdoMet or mineral oil. AdoMet lowered the pathology in CCl4-treated mice as shown by transaminase levels, hematoxylin and eosin, Masson's trichrome staining, and collagen I expression. beta-Galactosidase activity indicated activation of the COL1A2 promoter in stellate cells from CCl4-treated mice and repression of such activation by AdoMet. Lipid peroxidation, transforming growth factor-beta (TGFbeta) expression, and decreases in glutathione levels were prevented by AdoMet. Incubation of primary stellate cells with AdoMet down-regulated basal and TGFbeta-induced collagen I and alpha-smooth muscle actin proteins. AdoMet metabolites down-regulated collagen I protein and mRNA levels. AdoMet repressed basal and TGFbeta-induced reporter activity in stellate cells transfected with COL1A2 promoter deletion constructs. AdoMet blocked TGFbeta induction of the -378 bp region of the COL1A2 promoter and prevented the phosphorylation of extracellular signal-regulated kinase 1/2 and the binding of Sp1 to the TGFbeta-responsive element. These observations unveil a novel mechanism by which AdoMet could ameliorate liver fibrosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30963-74
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15983038-Animals, pubmed-meshheading:15983038-Base Sequence, pubmed-meshheading:15983038-Carbon Tetrachloride, pubmed-meshheading:15983038-Cells, Cultured, pubmed-meshheading:15983038-Collagen, pubmed-meshheading:15983038-Collagen Type I, pubmed-meshheading:15983038-Cytochrome P-450 CYP2E1, pubmed-meshheading:15983038-Fibrosis, pubmed-meshheading:15983038-Gene Expression Regulation, pubmed-meshheading:15983038-Genes, Reporter, pubmed-meshheading:15983038-Glutathione, pubmed-meshheading:15983038-Hepatocytes, pubmed-meshheading:15983038-Humans, pubmed-meshheading:15983038-Lipid Peroxidation, pubmed-meshheading:15983038-Liver, pubmed-meshheading:15983038-Mice, pubmed-meshheading:15983038-Mice, Transgenic, pubmed-meshheading:15983038-Molecular Sequence Data, pubmed-meshheading:15983038-Promoter Regions, Genetic, pubmed-meshheading:15983038-S-Adenosylmethionine, pubmed-meshheading:15983038-Transforming Growth Factor beta
pubmed:year
2005
pubmed:articleTitle
S-adenosylmethionine blocks collagen I production by preventing transforming growth factor-beta induction of the COL1A2 promoter.
pubmed:affiliation
Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA. natalia.nieto@mssm.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural