Leptin deficiency prevents the activation of the murine alpaha 2(I) collagen promoter by acetaldehyde.
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.
Potter
James J
JJ
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2195, USA.
Rennie-Tankersley
Lynda
L
Mezey
Esteban
E
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
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