Expression of pleiotrophin and its receptors in hepatic cells and in activated hepatic stellate cells (HSCs)– Pleiotrophin in hepatic stellate cells

Abstract

Pleiotrophin (PTN) is a heparin-binding protein and a growth factor with a broad spectrum of biological activities very similar to the Fibroblast Growth Factors (FGFs). FGFs and PTN promote the growth, survival, and migration of various cells, and play many roles in epithelial mesenchymal interactions during organogenesis. Particulary, expression of PTN has been implicated in the development and tissue repair of the liver. PTN interacts with several receptor proteins which may transduce PTN signaling in a cell type specific way. As PTN receptor has been proposed syndecan-3, receptor-tyrosine phosphatase (RPTP)zeta, anaplastic lymphoma kinase (ALK) and the Wnt co-receptors LRP5/6. Syndecan-3 and RPTPzeta have been proposed to be the receptor of PTN-induced neurite outgrowth, migration and survival of embryonic neurons. In this study we analysed the expression of PTN, the expression of the receptors ALK and LRP5/6 in rat liver cells, in activated rat hepatic stellate cells and in human and rat myofibroblasts. Ligand and receptor expression was investigated at the mRNA level using reverse transcription polymerase chain reaction. All analysed hepatic nonparenchymal cells including stellate cells, sinusoidal endothelial cells and Kupffer cells demonstrate PTN-, ALK- and LRP5/6- mRNA expression. Hepatocytes did not express the anaplastic lymphoma kinase. Interestingly, since ALK and PTN are implicated in tumor formation, ALK expression was also not detected in the hepatoma cell line HepG2. Since PTN prevents apoptosis in serum-starved NIH3T3 fibroblasts via activation of ALK at concentrations much lower than those needed to induce cell growth, the function of PTN in the diseased liver may mainly be its anti-apoptotic signaling in HSCs.