title: Adenovirus-mediated hepatic syndecan-1 overexpression induces hepatocyte proliferation and hyperlipidaemia in mice.
abstract: BACKGROUND
  Heparan sulfate proteoglycans (HSPGs) have been involved in the regulation of cell growth, apoptosis and lipid metabolism in vitro; however, their functional role in vivo remains unknown.
  
  
  OBJECTIVE
  Here, we describe hepatic tissue and lipid metabolism changes after liver overexpression of syndecan-1 (SDC-1), the main hepatic HSPG, in mice induced by adenoviral gene transfer.
  
  
  RESULTS
  SDC-1 overexpression was associated with marked hepatocyte proliferation, cell-isolated apoptosis and increased plasma alanine aminotransferase (ALT) levels. Additionally, SDC-1 liver overexpression significantly raised plasma cholesterol and triglyceride concentrations due to an increase in all lipoprotein particles, including the appearance of large and apolipoprotein (apo) E-enriched high-density lipoprotein (HDL) particles. Hepatic very low-density lipoprotein (VLDL) production was not affected by SDC-1 overexpression, suggesting a delayed plasma clearance of apo B lipoproteins as the underlying hyperlipidaemic mechanism. These pleotropic effects were qualitatively equivalent, even though less intense, in mice overexpressing a cytoplasmic C-terminal domain-deleted SDC-1.
  
  
  CONCLUSIONS
  This is the first report in vivo of the biological effects induced by a specific HSPG in the liver, with potential implications in both regenerative biology and molecular lipidology.
authors.affiliation: Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile.
authors.forename: Víctor
authors.initials: V
authors.lastname: Cortés
authors.forename: Ludwig
authors.initials: L
authors.lastname: Amigo
authors.forename: Katherine
authors.initials: K
authors.lastname: Donoso
authors.forename: Ilse
authors.initials: I
authors.lastname: Valencia
authors.forename: Verónica
authors.initials: V
authors.lastname: Quiñones
authors.forename: Silvana
authors.initials: S
authors.lastname: Zanlungo
authors.forename: Enrique
authors.initials: E
authors.lastname: Brandan
authors.forename: Attilio
authors.initials: A
authors.lastname: Rigotti
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D049109:Cell Proliferation; D006493:Heparin / Q000031:analogs & derivatives / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology*; D006949:Hyperlipidemias / Q000209:etiology*; D050356:Lipid Metabolism; D051379:Mice; D008822:Mice, Transgenic; D011509:Proteoglycans / Q000502:physiology; D053668:Syndecan-1 / Q000235:genetics* / Q000502:physiology*; D014162:Transfection / Q000379:methods
chemical_list: D011509:Proteoglycans; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; C036090:heparin proteoglycan; D006493:Heparin