Adenovirus-mediated hepatic syndecan-1 overexpression induces hepatocyte proliferation and hyperlipidaemia in mice.
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.
Cortés
Víctor
V
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile.
Amigo
Ludwig
L
Donoso
Katherine
K
Valencia
Ilse
I
Quiñones
Verónica
V
Zanlungo
Silvana
S
Brandan
Enrique
E
Rigotti
Attilio
A
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
D011509:Proteoglycans; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; C036090:heparin proteoglycan; D006493:Heparin