Linked Life Data

15708965

Source:http://linkedlifedata.com/resource/pubmed/id/15708965

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-5-17
pubmed:abstractText
The matrix protein fibronectin (FN) is a potent agoinst of vascular smooth muscle cell (SMC) migration. The role of rapamycin and the mammalian target of rapamycin (mTOR) in matrix protein-induced migration has not yet been defined. In these studies, we found that rapamycin (10 nM) markedly diminished chemotaxis of E47 cells (a cell line derived from human atherosclerotic plaques) and rat aortic SMCs toward FN as well as type I collagen and laminin; however, a period of preincubation >20 h was required. Subsequently, we showed that treatment with FN induced a rapid activation of mTOR as well as its downstream effector, S6 kinase (S6K). Moreover, FN-induced activation of both proteins was inhibited by preincubation with rapamycin for only 30 min. We then explored the upstream signaling pathway through which FN might mediate mTOR activation. A blocking antibody to alpha(v)beta(3) inhibited FN-induced mTOR/S6K activation as well as E47 cell chemotaxis, implicating alpha(v)beta(3) as the integrin receptor responsible for initiating FN-induced migration. Moreover, preincubation of E47 cells with wortmannin or LY-294002 blocked FN-induced mTOR/S6K activation, demonstrating that phosphatidylinositol 3-kinase (PI3K) plays a critical role in this rapamycin-sensitive signaling pathway. It has been previously suggested that rapamycin's effect on migration maybe related to enhancement of p27(kip1). However, treatment of E47 cells with rapamycin did not alter the level of p27(kip1) in the presence or absence of FN. Taken together, our data demonstrate that rapamycin inhibits FN-induced SMC migration through a pathway that involves at least alpha(v)beta(3)-integrin, PI3K, mTOR, and S6K.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
288
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H2861-8
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Rapamycin inhibits fibronectin-induced migration of the human arterial smooth muscle line (E47) through the mammalian target of rapamycin.
pubmed:affiliation
Dept. of Surgery, New York Presbyterian Hospital, 525 E. 68th St., Payson 707, New York, NY 10021, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural