Hepatocyte growth factor triggers signaling cascades mediating vascular smooth muscle cell migration

Taher E. I. Taher, Patrick W. B. Derksen, Onno J. de Boer, Marcel Spaargaren, Peter Teeling, Allard C. van der Wal, Steven T. Pals

Research output: Contribution to journalArticleAcademicpeer-review

34 Citations (Scopus)

Abstract

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 P13-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 beta1 integrins and required P13-K activation. Our results suggest a role for the HGF-Met signaling pathway in the pathogenesis of atherosclerosis and restenosis. (C) 2002 Elsevier Science (USA). All rights reserved
Original languageEnglish
Pages (from-to)80-86
JournalBiochemical and Biophysical Research Communications
Volume298
Issue number1
DOIs
Publication statusPublished - 2002

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