title: Leptin deficiency prevents the activation of the murine alpaha 2(I) collagen promoter by acetaldehyde.
abstract: Leptin enhances hepatic fibrosis induced experimentally by various agents. The influence of leptin deficiency on murine alpha 2(I) collagen promoter activation by acetaldehyde and by TGF beta 1 was investigated. Acetaldehyde failed to activate the promoter in ob/ob stellate cells as compared to its activating effect in wild-type cells. By contrast, TGF beta 1 increased the activity of the promoter in the ob/ob and wild-type cells. Total cell TGF beta 1 and secretion of total and free TGF beta 1 were lower in cultured stellate cells from ob/ob mice than wild-type mice. Acetaldehyde increased free cell TGF beta1 and secretion of total and free TGF beta 1 in wild-type, but not in ob/ob cells. The lack of activation of the alpha 2(I) collagen promoter by acetaldehyde in association with a lack of increase in TGF beta 1 in response to acetaldehyde in ob/ob stellate cells provides further evidence for a mediating role of TGF beta 1 in the actions of acetaldehyde on collagen transcription.
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2195, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Potter
authors.forename: Lynda
authors.initials: L
authors.lastname: Rennie-Tankersley
authors.forename: Esteban
authors.initials: E
authors.lastname: Mezey
mesh_terms: D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics*; D024042:Collagen Type I; D003470:Culture Media / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000172:deficiency* / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
chemical_list: D024042:Collagen Type I; D003470:Culture Media; D020738:Leptin; D012333:RNA, Messenger; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen; D008156:Luciferases; D000079:Acetaldehyde