TY - JOUR
T1 - Hepatocyte growth factor triggers signaling cascades mediating vascular smooth muscle cell migration
AU - Taher, Taher E.I.
AU - Derksen, Patrick W.B.
AU - De Boer, Onno J.
AU - Spaargaren, Marcel
AU - Teeling, Peter
AU - Van der Wal, Allard C.
AU - Pals, Steven T.
PY - 2002
Y1 - 2002
N2 - A key event in neointima formation and atherogenesis is the migration of vascular smooth muscle cells (VSMCs) into the intima. This is controlled by cytokines and extracellular matix (ECM) components within the microenvironment of the diseased vessel wall. At present, these signals have only been partially identified. In this study, we demonstrate that Met, the receptor tyrosine kinase for hepatocyte growth factor (HGF), is expressed on VSMCs isolated from the intima of atherosclerotic plaques of carotid arteries. Stimulation with HGF led to activation of Met as well as to activation of PI3-K, PKB/Akt, MEK, and the MAP kinases Erk1 and -2. Moreover, HGF induced lamellipodia formation, a characteristic feature of motile cells, and promoted VSMC migration across fibronectin-coated filters. The HGF-induced cell migration was mediated by β1 integrins and required PI3-K activation. Our results suggest a role for the HGF-Met signaling pathway in the pathogenesis of atherosclerosis and restenosis.
AB - A key event in neointima formation and atherogenesis is the migration of vascular smooth muscle cells (VSMCs) into the intima. This is controlled by cytokines and extracellular matix (ECM) components within the microenvironment of the diseased vessel wall. At present, these signals have only been partially identified. In this study, we demonstrate that Met, the receptor tyrosine kinase for hepatocyte growth factor (HGF), is expressed on VSMCs isolated from the intima of atherosclerotic plaques of carotid arteries. Stimulation with HGF led to activation of Met as well as to activation of PI3-K, PKB/Akt, MEK, and the MAP kinases Erk1 and -2. Moreover, HGF induced lamellipodia formation, a characteristic feature of motile cells, and promoted VSMC migration across fibronectin-coated filters. The HGF-induced cell migration was mediated by β1 integrins and required PI3-K activation. Our results suggest a role for the HGF-Met signaling pathway in the pathogenesis of atherosclerosis and restenosis.
KW - Atherosclerosis
KW - Hepatocyte growth factor
KW - Met
KW - Migration
KW - Vascular smooth muscle cell
UR - https://www.scopus.com/pages/publications/0036401153
U2 - 10.1016/S0006-291X(02)02397-5
DO - 10.1016/S0006-291X(02)02397-5
M3 - Article
C2 - 12379223
AN - SCOPUS:0036401153
SN - 0006-291X
VL - 298
SP - 80
EP - 86
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -