TY - JOUR
T1 - Reactive oxygen and NF-κB in VEGF-induced migration of human vascular smooth muscle cells
AU - Wang, Zhongbiao
AU - Castresana, Manuel R.
AU - Newman, Walter H.
N1 - Funding Information:
This work was supported in part by a grant from the MedCen Foundation and the Clinical Research Center of the Medical Center of Central Georgia. We thank Dr. M. Lienhard Schmitz (German Cancer Research Center, Heidelberg, Germany) for kindly providing plasmid RcCMV-IκB-αM and Benjamin Parrish Mitchell for his effort in the cell culture.
PY - 2001
Y1 - 2001
N2 - Migration and proliferation of vascular smooth muscle cells (VSMC) contribute to angiogenesis and the lesions of atherosclerosis. Since, vascular endothelial growth factor (VEGF) is overexpressed by VSMC in intima of atherosclerotic human coronary arteries, we determined if VEGF could stimulate VSMC migration and the intracellular signals involved. VEGF induced VSMC migration but had no significant activity on proliferation. VEGF increased intracellular reactive oxygen species (RES), NF-κB activation and IL-6 expression. Blockade of the generation of intracellular ROS by antioxidants inhibited VEGF-induced NF-κB activation, IL-6 expression, and cell migration indicating that generation of Res was required for NF-κB activation and the chemotactic activity of VEGF. Expression of a mutated, nondegradable form of inhibitor of NF-κB (IκB-αM) suppressed VEGF-triggered activation of NF-κB and upregulation of IL-6 as well as VSMC migration. Neutralization of IL-6 by its antibody significantly attenuated the migration stimulated by VEGF. Collectively, our data provide the first evidence that intracellular Res and NF-κB are required for VEGF-mediated smooth muscle cell migration. Further, IL-6 induced by VEGF is involved in the ability of the growth factor to stimulate migration.
AB - Migration and proliferation of vascular smooth muscle cells (VSMC) contribute to angiogenesis and the lesions of atherosclerosis. Since, vascular endothelial growth factor (VEGF) is overexpressed by VSMC in intima of atherosclerotic human coronary arteries, we determined if VEGF could stimulate VSMC migration and the intracellular signals involved. VEGF induced VSMC migration but had no significant activity on proliferation. VEGF increased intracellular reactive oxygen species (RES), NF-κB activation and IL-6 expression. Blockade of the generation of intracellular ROS by antioxidants inhibited VEGF-induced NF-κB activation, IL-6 expression, and cell migration indicating that generation of Res was required for NF-κB activation and the chemotactic activity of VEGF. Expression of a mutated, nondegradable form of inhibitor of NF-κB (IκB-αM) suppressed VEGF-triggered activation of NF-κB and upregulation of IL-6 as well as VSMC migration. Neutralization of IL-6 by its antibody significantly attenuated the migration stimulated by VEGF. Collectively, our data provide the first evidence that intracellular Res and NF-κB are required for VEGF-mediated smooth muscle cell migration. Further, IL-6 induced by VEGF is involved in the ability of the growth factor to stimulate migration.
KW - Interleukin 6
KW - Migration
KW - NF-κB
KW - Reactive oxygen species
KW - Vascular endothelial growth factor
KW - Vascular smooth muscle cell
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U2 - 10.1006/bbrc.2001.5232
DO - 10.1006/bbrc.2001.5232
M3 - Article
C2 - 11453645
AN - SCOPUS:0034804397
SN - 0006-291X
VL - 285
SP - 669
EP - 674
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -