Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-5-7
pubmed:abstractText
Recent studies suggest members of the degenerin (DEG)/epithelial Na(+) channel (ENaC)/acid-sensing ion channel (ASIC) protein family play an important role in vascular smooth muscle cell (VSMC) migration. In a previous investigation, we found suppression of a certain DEG/ENaC/ASIC member, ASIC2, increased VSMC chemotactic migration, raising the possibility that ASIC2 may play an inhibitory role. Because ASIC2 protein was retained in the cytoplasm, we reasoned increasing surface expression of ASIC2 might unmask the inhibitory role of ASIC2 in VSMC migration so we could test the hypothesis that ASIC2 inhibits VSMC migration. Therefore, we used the chemical chaperone glycerol to enhance ASIC2 expression. Glycerol 1) increased cytoplasm ASIC2 expression, 2) permitted detection of ASIC2 at the cell surface, and 3) inhibited platelet-derived growth factor (PDGF)-bb mediated VSMC migration. Furthermore, ASIC2 silencing completely abolished the inhibitory effect of glycerol on migration, suggesting upregulation of ASIC2 is responsible for glycerol-induced inhibition of VSMC migration. Because other investigators have shown that glycerol regulates ENaC/ASIC via interactions with a certain heat shock protein, heat shock protein 70 (Hsc70), we wanted to determine the importance of Hsc70 on ASIC2 expression in VSMCs. We found that Hsc70 silencing increases ASIC2 cell surface expression and inhibits VSMC migration, which is abolished by cosilencing ASIC2. These data demonstrate that Hsc70 inhibits ASIC2 expression, and, when the inhibitory effect of Hsc70 is removed, ASIC2 expression increases, resulting in reduced VSMC migration. Because VSMC migration contributes to vasculogenesis and remodeling following vascular injury, our findings raise the possibility that ASIC2-Hsc70 interactions may play a role in these processes.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/ASIC channel, http://linkedlifedata.com/resource/pubmed/chemical/Epithelial Sodium Channel, http://linkedlifedata.com/resource/pubmed/chemical/Glycerol, http://linkedlifedata.com/resource/pubmed/chemical/HSC70 Heat-Shock Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Hspa8 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering, http://linkedlifedata.com/resource/pubmed/chemical/Sodium Channels, http://linkedlifedata.com/resource/pubmed/chemical/degenerin epithelial sodium channels, http://linkedlifedata.com/resource/pubmed/chemical/platelet-derived growth factor BB
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
294
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H2022-30
pubmed:meshHeading
pubmed-meshheading:18310515-Animals, pubmed-meshheading:18310515-Cell Line, pubmed-meshheading:18310515-Cell Membrane, pubmed-meshheading:18310515-Cell Movement, pubmed-meshheading:18310515-Cytoplasm, pubmed-meshheading:18310515-Epithelial Sodium Channel, pubmed-meshheading:18310515-Glycerol, pubmed-meshheading:18310515-HSC70 Heat-Shock Proteins, pubmed-meshheading:18310515-Membrane Proteins, pubmed-meshheading:18310515-Muscle, Smooth, Vascular, pubmed-meshheading:18310515-Myocytes, Smooth Muscle, pubmed-meshheading:18310515-Nerve Tissue Proteins, pubmed-meshheading:18310515-Platelet-Derived Growth Factor, pubmed-meshheading:18310515-RNA, Small Interfering, pubmed-meshheading:18310515-RNA Interference, pubmed-meshheading:18310515-Rats, pubmed-meshheading:18310515-Signal Transduction, pubmed-meshheading:18310515-Sodium Channels, pubmed-meshheading:18310515-Up-Regulation
pubmed:year
2008
pubmed:articleTitle
Hsc70 regulates cell surface ASIC2 expression and vascular smooth muscle cell migration.
pubmed:affiliation
Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St., Jackson, MS 39216, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural