Source:http://linkedlifedata.com/resource/pubmed/id/17369292
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2007-6-11
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| pubmed:abstractText |
Idiopathic pulmonary arterial hypertension (IPAH) in human patients is associated with mutations in type 2 receptor for the bone morphogenic protein pathway (BMPR2). Mice expressing an inducible dominant negative form of BMPR2 in smooth muscle develop elevated right ventricular pressures when the transgene is activated. We hypothesized that transcriptional changes in these mice may allow insight into the early molecular events leading to IPAH. Microarray analysis was used to examine the transcriptional changes induced in whole lung by loss of normal smooth muscle cell (SMC) BMPR2 signaling in adult male or female mice (12 wk at time of death) expressing the transgene for either 1 or 8 wk. Our key results include a decrease in markers of smooth muscle differentiation, an increase in cytokines and markers of immune response, particularly in female mice, and a decrease in angiogenesis-related genes. These broad patterns of gene expression appear as early as 1 wk and are well established by 8 wk. Results were confirmed by quantitative RT-PCR to RNA from individual mice. Primary pulmonary artery SMC cultures transfected with small interfering RNA to BMPR2 also show loss of SMC markers myosin heavy chain 11 and calponin by quantitative RT-PCR and Western blot. These studies show classes of genes differentially regulated in response to loss of BMPR2 in SMC in vivo with clear relevance to the IPAH disease process, suggesting that the relevance of BMPR2 dysregulation may extend beyond proliferation.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers,
http://linkedlifedata.com/resource/pubmed/chemical/Bmpr2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Microfilament Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/transgelin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
1040-0605
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
292
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
L1556-63
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| pubmed:dateRevised |
2011-11-10
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| pubmed:meshHeading |
pubmed-meshheading:17369292-Animals,
pubmed-meshheading:17369292-Biological Markers,
pubmed-meshheading:17369292-Bone Morphogenetic Protein Receptors, Type II,
pubmed-meshheading:17369292-Cell Differentiation,
pubmed-meshheading:17369292-Cell Division,
pubmed-meshheading:17369292-Female,
pubmed-meshheading:17369292-Hypertension, Pulmonary,
pubmed-meshheading:17369292-Male,
pubmed-meshheading:17369292-Mice,
pubmed-meshheading:17369292-Mice, Transgenic,
pubmed-meshheading:17369292-Microfilament Proteins,
pubmed-meshheading:17369292-Muscle Proteins,
pubmed-meshheading:17369292-Myocytes, Smooth Muscle,
pubmed-meshheading:17369292-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:17369292-Pulmonary Artery,
pubmed-meshheading:17369292-Pulmonary Circulation,
pubmed-meshheading:17369292-RNA, Small Interfering,
pubmed-meshheading:17369292-Signal Transduction,
pubmed-meshheading:17369292-Transfection
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| pubmed:year |
2007
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| pubmed:articleTitle |
Molecular effects of loss of BMPR2 signaling in smooth muscle in a transgenic mouse model of PAH.
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| pubmed:affiliation |
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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