Upregulation of pleiotrophin expression in rat hepatic stellate cells by PDGF and hypoxia: Implications for its role in experimental biliary liver fibrogenesis

Pleiotrophin (PTN) is a secretory heparin binding protein with various biological activities including mitogenesis, angiogenesis, and tissue repair after injury. Recent studies have shown that PTN is a strong mitogen of hepatocytes and involved in liver regeneration. In adult liver cells Ptn gene is mainly expressed by quiescent hepatic stellate cells (HSCs). Although we have been able to demonstrate mRNA and protein expression of the anaplastic lymphoma kinase-the receptor tyrosine kinase for PTN-on HSCs, PTN did not act as a mitogen of HSCs in contrast to hepatocytes. PTN immunoreactivity was markedly increased in experimental fibrogenesis by common bile duct ligation and observed in sinusoidal HSCs. In primary HSC cultures, Ptn transcription was significantly increased by PDGF-BB, and under hypoxic atmosphere. Mechanistically, hypoxia and PDGF mediated induction of PTN expression in sinusoidal HSCs may provide a strong mitogenic signal for hepatocytes to limit the damage to the parenchymal cells in biliary-type liver fibrogenesis.