title: Role of the receptor for advanced glycation end products in hepatic fibrosis.
abstract: OBJECTIVE
  To study the role of advanced glycation end products (AGE) and their specific receptor (RAGE) in the pathogenesis of liver fibrogenesis.
  
  
  METHODS
  In vitro RAGE expression and extracellular matrix-related gene expression in both rat and human hepatic stellate cells (HSC) were measured after stimulation with the two RAGE ligands, advanced glycation end product-bovine serum albumin (AGE-BSA) and N(epsilon)-(carboxymethyl) lysine (CML)-BSA, or with tumor necrosis factor-alpha (TNF-alpha). In vivo RAGE expression was examined in models of hepatic fibrosis induced by bile duct ligation or thioacetamide. The effects of AGE-BSA and CML-BSA on HSC proliferation, signal transduction and profibrogenic gene expression were studied in vitro.
  
  
  RESULTS
  In hepatic fibrosis, RAGE expression was enhanced in activated HSC, and also in endothelial cells, inflammatory cells and activated bile duct epithelia. HSC expressed RAGE which was upregulated after stimulation with AGE-BSA, CML-BSA, and TNF-alpha. RAGE stimulation with AGE-BSA and CML-BSA did not alter HSC proliferation, apoptosis, fibrogenic signal transduction and fibrosis- or fibrolysis-related gene expression, except for marginal upregulation of procollagen alpha1(I) mRNA by AGE-BSA.
  
  
  CONCLUSIONS
  Despite upregulation of RAGE in activated HSC, RAGE stimulation by AGE does not alter their fibrogenic activation. Therefore, RAGE does not contribute directly to hepatic fibrogenesis.
authors.affiliation: Department of Medicine I, University of Erlangen-Nuremberg, Erlangen-Nürnberg, D-91054, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Lohwasser
authors.forename: Daniel
authors.initials: D
authors.lastname: Neureiter
authors.forename: Yury
authors.initials: Y
authors.lastname: Popov
authors.forename: Michael
authors.initials: M
authors.lastname: Bauer
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
mesh_terms: D000818:Animals; D002417:Cattle; D049109:Cell Proliferation; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases