A new signaling mechanism of hepatocyte growth factor‐induced endothelial proliferation

Abstract

Summary. Background: The hepatocyte growth factor (HGF) has been shown to promote endothelial cell proliferation. In this study, the signaling cascade responsible for the HGF-induced proliferation was examined. Methods: The proliferation of human umbilical cord vein endothelial cells (HUCVEC) was determined using cell counts. Changes of the membrane potential were analyzed using the fluorescence dye DiBAC. Intracellular cGMP-levels were measured by means of [ ). A HGF-induced hyperpolarization that was blocked by iberiotoxin was observed. In addition, HGF-induced activation of the eNOS was blocked by the K + channel inhibitor. An increase of +101% MAPK phosphorylation was induced by HGF, which was blocked, if the cells were treated with L-NMMA (n ¼ 20; P < 0.05), whereas HGF-induced phosphorylation of the eNOS was not affected by MEK inhibition. Conclusions: Hepatocyte growth factor modulates endothelial K + channels causing an activation of the eNOS; the increase of nitric oxide is necessary for the phosphorylation of the MAPK inducing the proliferation of HUCVEC.

Migration of oral squamous cell carcinoma cells are induced by HGF/c-Met signalling via lamellipodia and filopodia formation

“…It has been reported that EGFR and c-Met are involved in cell migration (20,(35)(36)(37)(38). In the present study, we showed that migration of the OSCC cell lines SAS and Ca9-22 was regulated by both the EGFR and c-Met signalling pathways.…”

Hepatocyte Growth Factor Regulates Migration of Olfactory Interneuron Precursors in the Rostral Migratory Stream through Met-Grb2 Coupling

“…Because HGF-induced MAP kinase cascade activation had been demonstrated to trigger a proliferation response in other brain regions (Ieraci et al, 2002;Kuhlmann et al, 2005), the . HGF is a chemoattractant for RMS neuroblasts.…”

Role of c-Met/Phosphatidylinositol 3-Kinase (PI3k)/Akt Signaling in Hepatocyte Growth Factor (HGF)-mediated Lamellipodia Formation, Reactive Oxygen Species (ROS) Generation, and Motility of Lung Endothelial Cells

“…HGF, also known as scatter factor, is the natural ligand for the receptor tyrosine kinase, c-Met (6) that is expressed on a variety of cell types including vascular endothelial cells and is up-regulated during angiogenesis (7,8). HGF interacts with its cognate receptor c-Met and promotes angiogenesis by enhancing the expression of vascular endothelial growth factor, one of the principal mediators of angiogenesis.…”

“…HGF interacts with its cognate receptor c-Met and promotes angiogenesis by enhancing the expression of vascular endothelial growth factor, one of the principal mediators of angiogenesis. HGF binding to c-Met triggers a cascade of signal transduction pathways including activation of phosphatidylinositol 3-kinase (PI3k) and Akt, which have been implicated in cell migration (7)(8)(9)(10)(11).…”

“…Cell migration is essential for embryonic development, wound healing, and angiogenesis (3,7,8,(12)(13)(14). It is a multistep process facilitated by highly coordinated cytoskeletal changes, including extracellular adhesion, plasma membrane protrusion at the leading edge (lamellipodia formation), formation of new adhesion sites under the protrusion, and disruption * This work was supported in part by Grants P01 HL098050 (to V. N.) and of older adhesions at the rear and contraction, thereby drawing the cell forward (12)(13)(14)(15)(16)(17)(18)(19)(20).…”