Linked Life Data

21730297

Source:http://linkedlifedata.com/resource/pubmed/id/21730297

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-7-21
pubmed:abstractText
The mast cell product, tryptase, has recently been implicated to mediate fibrosis in the hypertensive heart. Tryptase has been shown to mediate noncardiac fibroblast function via activation of protease-activated receptor 2 and subsequent activation of the mitogen-activated protein kinase pathway, including extracellular signal-regulated kinase 1/2. Therefore, we hypothesized that this pathway may be a mechanism leading to fibrosis in the hypertensive heart. Isolated adult cardiac fibroblasts were treated with tryptase, which induced activation of extracellular signal-regulated kinase 1/2 via protease-activated receptor 2. Blockade of protease activated receptor 2 with FSLLRY (10 ?mol/L) and inhibition of the extracellular signal-regulated kinase pathway with PD98059 (10 ?mol/L) prevented collagen synthesis in isolated cardiac fibroblasts stimulated with tryptase. In contrast, p38 mitogen-activated protein kinase and stress-activated protein/c-Jun N-terminal kinase were not activated by tryptase. Cardiac fibroblasts isolated from spontaneously hypertensive rats showed this same pattern of activation. Treatment of spontaneously hypertensive rats with FSLLRY prevented fibrosis in these animals, indicating the in vivo applicability of the cultured fibroblast findings. Also, tryptase induced a myofibroblastic phenotype indicated by elevations in ?-smooth muscle actin and extra type III domain A (ED-A) fibronectin. Thus, the results from this study demonstrate the importance of tryptase for inducing a cardiac myofibroblastic phenotype, ultimately leading to the development of cardiac fibrosis. Specifically, tryptase causes cardiac fibroblasts to increase collagen synthesis via a mechanism involving activation of protease-activated receptor 2 and subsequent induction of extracellular signal-regulated kinase signaling.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
264-70
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Tryptase/Protease-activated receptor 2 interactions induce selective mitogen-activated protein kinase signaling and collagen synthesis by cardiac fibroblasts.
pubmed:affiliation
Cell Biology and Anatomy, School of Medicine, University of South Carolina, 6349 Garners Ferry Rd, Columbia, SC 29208, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural