Linked Life Data

16585062

Source:http://linkedlifedata.com/resource/pubmed/id/16585062

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2006-5-5
pubmed:abstractText
Fibroblasts and myofibroblasts both participate in wound healing. Transforming growth factor beta (TGFbeta) induces fibroblasts to differentiate into myofibroblasts, whereas fibroblast growth factor and heparin (FGF/h) induce myofibroblasts to "de-differentiate" into fibroblasts. TGFbeta induces expression of smooth muscle alpha actin (SMalphaA) and incorporation into in stress fibers, a phenotype of differentiated myofibroblasts. Additionally, TGFbeta induces the expression of fibronectin and fibronectin integrins. Fibronectin-generated signals contribute to the TGFbeta-mediated myofibroblast differentiation. Because fibronectin signals are transmitted through focal adhesion kinase (FAK), it was predicted that FAK would be essential to TGFbeta-mediated myofibroblast differentiation. To determine whether the FAK signaling pathway is required for myofibroblast differentiation, we used two approaches to decrease FAK in mouse embryo fibroblasts (MEFs): 1) FAK +/+ MEFs, in which FAK protein expression was greatly decreased by short hairpin RNA (shRNA), and 2) FAK -/- MEFs, which lack FAK. In both cases, the majority of cells were myofibroblasts, expressing SMalphaA in stress fibers even after treatment with FGF/h. Furthermore, both the surface expression of FGFRs and FGF signaling were greatly reduced in FAK -/- [corrected]MEFs. We conclude that FAK does not contribute to TGFbeta-dependent myofibroblast differentiation. Instead, FAK was necessary for FGF/h signaling in down-regulating expression of SMalphaA, which is synonymous with myofibroblast differentiation. FAK activation could contribute to regulating myofibroblast differentiation, thereby ameliorating fibrosis.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1006-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
FAK-dependent regulation of myofibroblast differentiation.
pubmed:affiliation
Department of Ophthalmology, Box 1183, Mount Sinai School of Medicine, 1 Gustave Levy Pl., New York, New York 10029-6574, USA. roseanne.greenberg@mssm.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural