Linked Life Data

21051861

Source:http://linkedlifedata.com/resource/pubmed/id/21051861

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2010-12-16
pubmed:abstractText
Epithelial-mesenchymal transition (EMT) has emerged as a major mechanism in the pathogenesis of organ fibrosis. The epithelium has been proposed to be a significant source of matrix-producing fibroblasts and of myofibroblasts (MFs), a motile and contractile cell type hallmarked by the expression of ?-smooth muscle actin (SMA). Importantly, tissue accumulation of MFs shows strong correlation with the severity and progression of fibrotic diseases. The pleiotropic cytokine transforming growth factor-?(1) has been long known as the chief inducer of fibrosis, EMT and MF generation. Accordingly, receptor Smads (Smad2 and particularly Smad3), the direct targets of the activated transforming growth factor-? receptor have been implicated as critical mediators in fibrogenesis and EMT. However, evidence is accumulating that the role of Smad3 is complex and apparently controversial; in fact, Smad3 may differentially affect the various components of EMT, including the loss of epithelial markers (de-epithelialization), the production of extracellular matrix (fibrogenesis) and the expression of SMA (myogenic program). In this review, we revisit the role of Smad3 in epithelial-myofibroblast transition (EMyT). We first summarize the evidence supporting the thesis that Smad3 is a key mediator of EMT and MF generation; next, we present evidence supporting the antithesis that Smad3 is in fact a negative regulator of SMA expression and the activation of the myogenic program in the epithelium; finally, we propose a synthesis, which depicts Smad3 as a timekeeper and context-dependent modulator of EMyT. We suggest that EMyT is composed of an early, mesenchymal, Smad3-promoted phase and a late, myogenic, Smad3-inhibitable phase.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1422-6421
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 S. Karger AG, Basel.
pubmed:issnType
Electronic
pubmed:volume
193
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
41-52
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Smaddening complexity: the role of Smad3 in epithelial-myofibroblast transition.
pubmed:affiliation
Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Department of Surgery, University of Toronto, Toronto, Ont., Canada.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't