Copyright © 2007, European Society of Cardiology
Syk contributes to PDGF-BB-mediated migration of rat aortic smooth muscle cells via MAPK pathways
aDepartments of Physiology and Immunology, College of Medicine, Konkuk University, Danwol-dong 322, Chungju 380-701, Republic of Korea
bDivision of Life Science, Konkuk University, Danwol-dong 322, Chungju 380-701, Republic of Korea
cDepartment of Physiology, Chungnam National University, Taejeon 301-131, Republic of Korea
* Corresponding author. Tel.: +82 43 8403726; fax: +82 43 8519329. Email address: bkkim2{at}kku.ac.kr
Objective: Here we investigated the role of spleen tyrosine kinase (Syk) in the migration induced by platelet-derived growth factor (PDGF) in rat aortic smooth muscle cells (RASMC).
Methods: Cell migration was determined using a Boyden chamber, by wound-healing, and by aortic ring assays. Activity of Syk, mitogen-activated protein kinase (MAPK), and heat shock protein 27 (HSP27) were tested using immunoblotting with kinase inhibitors and small interference RNAs.
Results: PDGF-BB induced binding of Syk to the PDGFβ receptor and increased the phosphorylation of Syk and migration in RASMC. These effects of PDGF-BB were inhibited by piceatannol, an inhibitor of Syk. PDGF-BB increased the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38 MAPK, and HSP27, which were significantly inhibited by piceatannol and in Syk-knockdown cells. The p38 MAPK inhibitor SB203580 and ERK1/2 inhibitor PD98059 inhibited the migration, which was further inhibited by the combination of these inhibitors. SB203580, but not PD98059, inhibited the phosphorylation of HSP27 induced by PDGF-BB in RASMC. PDGF-BB-induced migration was attenuated in HSP27-knockdown cells. Kinase inhibitors and Syk-knockdown diminished PDGF-BB-induced sprout outgrowth in the aortic ring assay.
Conclusions: These results imply that Syk is an upstream signal of the p38 MAPK/HSP27 and ERK1/2 pathways that contributes to PDGF-BB-mediated migration in RASMC.
KEYWORDS Smooth muscle; Growth factor; MAP kinase; Tyrosine protein kinase; Remodeling
1 Contributed equally to the manuscript.
Time for primary review 34 days
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