Carloni V, Romanelli R G, Pinzani M, Laffi G, Gentilini P
Istituto di Medicina Interna, Universitá di Firenze, Italy.
Gastroenterology. 1997 Feb;112(2):522-31. doi: 10.1053/gast.1997.v112.pm9024306.
BACKGROUND & AIMS: Hepatic stellate cells (HSCs) play a key role in the development of liver fibrosis. Integrin receptors contribute to the regulation cell adhesion and migration. The aim of this study was to evaluate the interaction between focal adhesion kinase (FAK) and phospholipase C gamma (PLC gamma) potentially involved in HSC integrin-mediated signaling pathways.
Interaction between FAK and PLC gamma was determined by immunoprecipitation and immunoblotting. HSC chemotactic activity was evaluated using the Boyden chamber technique.
HSC adhesion to extracellular matrix components (collagen type I and IV, laminin, and fibronectin) and antibody-mediated beta 1 ligation elicited increased tyrosine phosphorylation of FAK. HSC adhesion to different extracellular matrix components did not result in PLC gamma tyrosine phosphorylation. However, HSC adhesion induced association between PLC gamma and FAK. All extracellular matrix components tested stimulated HSC chemotactic activity only at high concentrations. On the contrary, platelet-derived growth factor, homodimer BB (PDGF-BB), was able 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.
These findings provide the first evidence that PLC gamma recruitment by FAK during HSC adhesion is an important process implicating a link between integrin and PDGF-mediated signaling pathways to regulate HSC adhesion and motility.
肝星状细胞（HSCs）在肝纤维化发展过程中起关键作用。整合素受体有助于调节细胞黏附和迁移。本研究旨在评估黏着斑激酶（FAK）与磷脂酶Cγ（PLCγ）之间的相互作用，这可能涉及肝星状细胞整合素介导的信号通路。
通过免疫沉淀和免疫印迹法确定FAK与PLCγ之间的相互作用。使用博伊登室技术评估肝星状细胞的趋化活性。
肝星状细胞与细胞外基质成分（I型和IV型胶原、层粘连蛋白和纤连蛋白）的黏附以及抗体介导的β1连接可引起FAK酪氨酸磷酸化增加。肝星状细胞与不同细胞外基质成分的黏附并未导致PLCγ酪氨酸磷酸化。然而，肝星状细胞黏附诱导了PLCγ与FAK之间的结合。所有测试的细胞外基质成分仅在高浓度时刺激肝星状细胞趋化活性。相反，血小板衍生生长因子同源二聚体BB（PDGF-BB）能够以剂量依赖方式刺激肝星状细胞迁移；这一事件在FAK磷酸化存在的情况下发生，与剂量依赖的PLCγ酪氨酸磷酸化相关。
这些发现首次证明，肝星状细胞黏附过程中FAK招募PLCγ是一个重要过程，涉及整合素和PDGF介导的信号通路之间的联系，以调节肝星状细胞的黏附和运动。
