FOCAL ADHESION KINASE AND PHOSPHOLIPASE C-GAMMA INVOLVEMENT IN ADHESION AND MIGRATION OF HUMAN HEPATIC STELLATE CELLS

Background & Aims: Hepatic stellate cells (HSCs) play a key role in th e development of liver fibrosis, Integrin receptors contribute to the regulation cell adhesion and migration. The aim of this study was to e valuate the interaction between focal adhesion kinase (FAK) and phosph olipase C gamma (PLC gamma) potentially involved in HSC integrin-media ted signaling pathways. Methods: Interaction between FAK and PLC gamma was determined by immunoprecipitation and immunoblotting. HSC chemota ctic activity was evaluated using the Boyden chamber technique, Result s: HSC adhesion to extracellular matrix components (collagen type I an d IV, laminin, and fibronectin) and antibody-mediated beta(1) ligation elicited increased tyrosine phosphorylation of FAK. HSC adhesion to d ifferent extracellular matrix components did not result in PLC gamma t yrosine phosphorylation. However, HSC adhesion induced association bet ween PLC gamma and FAK. All extracellular matrix components tested sti mulated HSC chemotactic activity only at high concentrations, On the c ontrary, platelet-derived growth factor, homodimer BE (PDGF-BB), was a ble to stimulate HSC migration in a dose-dependent manner; this event, occurring in the presence of FAK phosphorylation, was associated to a dose-dependent PLC gamma tyrosine phosphorylation. Conclusions: These findings provide the first evidence that PLC gamma recruitment by FAK during HSC adhesion is an important process implicating a link betwee n integrin and PDGF-mediated signaling pathways to regulate HSC adhesi on and motility.