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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2003-1-16
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pubmed:abstractText |
Capacitative Ca(2+) entry (CCE) through store-operated Ca(2+) (SOC) channels plays an important role in returning Ca(2+) to the sarcoplasmic reticulum (SR) and regulating cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)). A rise in [Ca(2+)](cyt) and sufficient Ca(2+) in the SR are required for pulmonary artery smooth muscle cell (PASMC) proliferation. We tested the hypothesis that platelet-derived growth factor (PDGF)-mediated PASMC growth involves upregulation of c-Jun and TRPC6, a transient receptor potential cation channel. In rat PASMC, PDGF (10 ng/ml for 0.5-48 h) phosphorylated signal transducer and activator of transcription (STAT3), increased mRNA and protein levels of c-Jun, and stimulated cell proliferation. PDGF treatment also upregulated TRPC6 expression and augmented CCE, elicited by passive depletion of Ca(2+) from the SR using cyclopiazonic acid. Furthermore, overexpression of c-Jun stimulated TRPC6 expression and CCE amplitude in PASMC. Downregulation of TRPC6 using an antisense oligonucleotide specifically for human TRPC6 decreased CCE and inhibited PDGF-mediated PASMC proliferation. These results suggest that PDGF-mediated PASMC proliferation is associated with c-Jun/STAT3-induced upregulation of TRPC6 expression. The resultant increase in CCE raises [Ca(2+)](cyt), facilitates return of Ca(2+) to the SR, and enhances PASMC growth.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Transporting ATPases,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Serum-Free,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Sarcoplasmic Reticulum...,
http://linkedlifedata.com/resource/pubmed/chemical/Stat3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/TRPC Cation Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0363-6143
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
284
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
C316-30
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12529250-Animals,
pubmed-meshheading:12529250-Calcium,
pubmed-meshheading:12529250-Calcium Channel Blockers,
pubmed-meshheading:12529250-Calcium Channels,
pubmed-meshheading:12529250-Calcium Signaling,
pubmed-meshheading:12529250-Calcium-Transporting ATPases,
pubmed-meshheading:12529250-Cell Division,
pubmed-meshheading:12529250-Cells, Cultured,
pubmed-meshheading:12529250-Culture Media, Serum-Free,
pubmed-meshheading:12529250-DNA-Binding Proteins,
pubmed-meshheading:12529250-Enzyme Inhibitors,
pubmed-meshheading:12529250-Gene Expression Regulation,
pubmed-meshheading:12529250-Genetic Vectors,
pubmed-meshheading:12529250-Lung,
pubmed-meshheading:12529250-Male,
pubmed-meshheading:12529250-Muscle, Smooth, Vascular,
pubmed-meshheading:12529250-Platelet-Derived Growth Factor,
pubmed-meshheading:12529250-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:12529250-Pulmonary Artery,
pubmed-meshheading:12529250-RNA, Messenger,
pubmed-meshheading:12529250-Rats,
pubmed-meshheading:12529250-Rats, Sprague-Dawley,
pubmed-meshheading:12529250-STAT3 Transcription Factor,
pubmed-meshheading:12529250-Sarcoplasmic Reticulum Calcium-Transporting ATPases,
pubmed-meshheading:12529250-TRPC Cation Channels,
pubmed-meshheading:12529250-Trans-Activators,
pubmed-meshheading:12529250-Up-Regulation
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pubmed:year |
2003
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pubmed:articleTitle |
PDGF stimulates pulmonary vascular smooth muscle cell proliferation by upregulating TRPC6 expression.
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pubmed:affiliation |
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Diego, California 92103, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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