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. AIM: 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.