Journal article
Gene Transfer of Redox Factor-1 Inhibits Neointimal Formation: Involvement of Platelet-Derived Growth Factor-β Receptor Signaling via the Inhibition of the Reactive Oxygen Species–Mediated Syk Pathway
Circulation research, Vol.104(2), pp.219-227
01/30/2009
DOI: 10.1161/CIRCRESAHA.108.178699
PMID: 19038866
Abstract
The role of apurinic/apyrimidinic endonuclease-1/redox factor-1 (Ref-1) in vascular smooth muscle cells has yet to be clearly elucidated. Therefore, we attempted to determine the roles of Ref-1 in the migration induced by platelet-derived growth factor (PDGF)-BB and in its signaling in rat aortic smooth muscle cells (RASMCs). Cellular migration, superoxide (O2) production, Rac-1 activity, and neointima formation were determined in cells transfected with adenoviruses encoding for Ref-1 (AdRef-1) and small interference RNA of Ref-1. Overexpression of Ref-1 induced by treatment with RASMCs coupled with AdRef-1 inhibited the migration induced by PDGF-BB. PDGF-BB also increased the phosphorylation of the PDGFβ receptor, spleen tyrosine kinase (Syk), mitogen-activated protein kinase, and heat shock protein 27, but these increases were significantly inhibited by AdRef-1 treatment. PDGF-BB increased O2 production and Rac-1 activity, and these were diminished in cells transfected with AdRef-1. In contrast, RASMC migration, phosphorylation of Syk and O2 production in response to PDGF-BB were increased by the knock down of Ref-1 with small interference RNA. The phosphorylation of PDGFβ receptor in response to PDGF-BB was inhibited completely by the Syk inhibitor and was partly attenuated by a NADPH oxidase inhibitor. PDGF-BB increased the sprout outgrowth of the aortic ring ex vivo, which was inhibited in the AdRef-1–infected RASMCs as compared with the controls. Balloon injury–induced neointimal formation was significantly attenuated by the gene transfer of AdRef-1. These results indicate that Ref-1 inhibits the PDGF-mediated migration signal via the inhibition of reactive oxygen species–mediated Syk activity in RASMCs.
Details
- Title: Subtitle
- Gene Transfer of Redox Factor-1 Inhibits Neointimal Formation: Involvement of Platelet-Derived Growth Factor-β Receptor Signaling via the Inhibition of the Reactive Oxygen Species–Mediated Syk Pathway
- Creators
- Hwan Lee - From the Institute of Medical Sciences (H.M.L., K.-J.W., C.-K.L., T.-K.P., W.S.C., Y.M.B., S.H.P., B.K.), School of Medicine, Konkuk University, Danwol-dong, Chungju, South Korea; Infection Signaling Network Research Center (B.H.J., H.S.K., S.K.L.), Department of Physiology, Chungnam National University, South Korea; and Cardiovascular Institute (K.I.), University of Pittsburgh Medical Center, PaByeong JeonKyung-Jong WonChang-Kwon LeeTae-Kyu ParkWahn ChoiYoung BaeHyo KimSang LeeSeung ParkKaikobad IraniBokyung Kim
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.104(2), pp.219-227
- Publisher
- American Heart Association, Inc
- DOI
- 10.1161/CIRCRESAHA.108.178699
- PMID
- 19038866
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 01/30/2009
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984047709402771
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