Source:http://linkedlifedata.com/resource/pubmed/id/20307651
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2010-5-11
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| pubmed:abstractText |
Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes to intima formation after stenting and balloon angioplasty. Pin1, a peptidyl prolyl isomerase recognizing phosphorylated Ser/Thr-Pro, isomerizes the peptide bond. Because Pin1 overexpression is associated with transformation and the uncontrolled cell growth of tumors, we hypothesized that Pin1 functions as a chronic stimulator of VSMC proliferation. Pin1-positive smooth muscle cells were seen in the neointimal region of the femoral artery after guidewire injury. Exposure of VSMCS to platelet-derived growth factor (PDGF) increased Pin1 expression in a concentration-dependent manner. Basal cell growth rate and cyclin D1 expression were enhanced in Pin1-overexpressing VSMCs (Pin1-VSMCs). Moreover, PDGF-induced production of reactive oxygen species (ROS) in Pin1-VSMCs was higher than in control VSMCs. In Pin1-VSMCs, heme oxygenase-1 (HO-1) induction in response to nitric oxide donor was suppressed compared to control VSMCs. Nuclear translocation of nuclear factor E2-related factor-2 (Nrf2) was also diminished in Pin1-VSMCs. In contrast, the activity of the inducible minimal antioxidant response element (ARE) was potentiated in Pin1-null mouse embryonic fibroblasts (MEFs), compared to Pin1-wild-type MEFs. Moreover, Nrf2 ubiquitination was stimulated by Pin1 overexpression. Intraperitoneal injection of juglone (a Pin1 inhibitor) for 3weeks (1mg/kg, two times a week) significantly suppressed neointimal formation induced by wire injury. In conclusion, Pin1 induction during neointimal formation may be associated with ROS-mediated VSMC proliferation via down-regulation of Nrf2/ARE-dependent HO-1 expression. Pin1 may be a novel therapeutic target for several vascular diseases including atherosclerosis and stenosis.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
1873-4596
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| pubmed:author | |
| pubmed:copyrightInfo |
(c) 2010 Elsevier Inc. All rights reserved.
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| pubmed:issnType |
Electronic
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| pubmed:day |
15
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| pubmed:volume |
48
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1644-53
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| pubmed:meshHeading |
pubmed-meshheading:20307651-Animals,
pubmed-meshheading:20307651-Cell Proliferation,
pubmed-meshheading:20307651-Down-Regulation,
pubmed-meshheading:20307651-Femoral Artery,
pubmed-meshheading:20307651-Gene Expression,
pubmed-meshheading:20307651-Gene Expression Regulation,
pubmed-meshheading:20307651-Heme Oxygenase-1,
pubmed-meshheading:20307651-Immunoblotting,
pubmed-meshheading:20307651-Immunohistochemistry,
pubmed-meshheading:20307651-Immunoprecipitation,
pubmed-meshheading:20307651-Male,
pubmed-meshheading:20307651-Mice,
pubmed-meshheading:20307651-Muscle, Smooth, Vascular,
pubmed-meshheading:20307651-Myocytes, Smooth Muscle,
pubmed-meshheading:20307651-NF-E2-Related Factor 2,
pubmed-meshheading:20307651-Peptidylprolyl Isomerase,
pubmed-meshheading:20307651-Rats,
pubmed-meshheading:20307651-Rats, Sprague-Dawley,
pubmed-meshheading:20307651-Reactive Oxygen Species,
pubmed-meshheading:20307651-Tunica Intima
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| pubmed:year |
2010
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| pubmed:articleTitle |
Role of Pin1 in neointima formation: down-regulation of Nrf2-dependent heme oxygenase-1 expression by Pin1.
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| pubmed:affiliation |
BK21 Project Team, College of Pharmacy, Chosun University, Gwangju 501-759, South Korea.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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