REGULATION OF PLATELET-DERIVED GROWTH-FACTOR SECRETION AND GENE-EXPRESSION IN HUMAN LIVER FAT-STORING CELLS

Background/Aims: Liver fat-storing cells (FSCs) actively proliferate and secrete extracellular matrix during liver injury. Platelet-derived growth factor (PDGF) is a potent mitogen for cultured FSCs. In the present study, we investigated the regulation of PDGF gene expression and production in cultured human liver FSCs. Methods: PDGF A-chain and B-chain expression was analyzed by Northern blotting and ribonuclease protection assay, respectively. Secretion of PDGF was evaluated by immunoprecipitation and immunoblotting of conditioned medium and metabolic labeling of FSC followed by immunoprecipitation. Results: Three PDGF A-chain transcripts were detectable. Stimulation of FSC with phorbol myristate acetate (10(-7) mol/L) or PDGF BB (20 ng/mL) increased steady-state levels of PDGF A-chain and B-chain messenger RNA. PDGF AA had a small stimulatory effect on A-chain but not B-chain messenger RNA levels. FSCs secrete PDGF in the conditioned medium. The secreted protein is bioactive, because concentrated conditioned medium induced an increase in thymidine incorporation that was inhibited by anti-PDGF antibodies. Conclusions: This study shows that cultured FSCs express PDGF A- and B-chain genes and release bioactive PDGF in the culture medium. These data raise the possibility of an autocrine or short-loop paracrine effect of PDGF in FSCs as a mechanism contributing to the maintenance of the proliferative state during liver injury.