Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-10-5
pubmed:abstractText
During embryogenesis the heart valves develop from undifferentiated mesenchymal endocardial cushions (EC), and activated interstitial cells of adult diseased valves share characteristics of embryonic valve progenitors. Twist1, a class II basic-helix-loop-helix (bHLH) transcription factor, is expressed during early EC development and is down-regulated later during valve remodeling. The requirements for Twist1 down-regulation in the remodeling valves and the consequences of prolonged Twist1 activity were examined in transgenic mice with persistent expression of Twist1 in developing and mature valves. Persistent Twist1 expression in the remodeling valves leads to increased valve cell proliferation, increased expression of Tbx20, and increased extracellular matrix (ECM) gene expression, characteristic of early valve progenitors. Among the ECM genes predominant in the EC, Col2a1 was identified as a direct transcriptional target of Twist1. Increased Twist1 expression also leads to dysregulation of fibrillar collagen and periostin expression, as well as enlarged hypercellular valve leaflets prior to birth. In human diseased aortic valves, increased Twist1 expression and cell proliferation are observed adjacent to nodules of calcification. Overall, these data implicate Twist1 as a critical regulator of valve development and suggest that Twist1 influences ECM production and cell proliferation during disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers, http://linkedlifedata.com/resource/pubmed/chemical/Col2a1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Collagen Type II, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/T-Box Domain Proteins, http://linkedlifedata.com/resource/pubmed/chemical/TWIST1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Tbx20 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Tek protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Twist Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/Twist1 protein, mouse
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1095-564X
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
347
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
167-79
pubmed:dateRevised
2011-11-1
pubmed:meshHeading
pubmed-meshheading:20804746-Animals, pubmed-meshheading:20804746-Animals, Newborn, pubmed-meshheading:20804746-Base Sequence, pubmed-meshheading:20804746-Biological Markers, pubmed-meshheading:20804746-Calcinosis, pubmed-meshheading:20804746-Cardiomyopathies, pubmed-meshheading:20804746-Cell Proliferation, pubmed-meshheading:20804746-Collagen Type II, pubmed-meshheading:20804746-Extracellular Matrix, pubmed-meshheading:20804746-Gene Expression Regulation, Developmental, pubmed-meshheading:20804746-Heart Valve Diseases, pubmed-meshheading:20804746-Heart Valves, pubmed-meshheading:20804746-Humans, pubmed-meshheading:20804746-Introns, pubmed-meshheading:20804746-Mice, pubmed-meshheading:20804746-Molecular Sequence Data, pubmed-meshheading:20804746-Morphogenesis, pubmed-meshheading:20804746-Nuclear Proteins, pubmed-meshheading:20804746-Protein Binding, pubmed-meshheading:20804746-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:20804746-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:20804746-T-Box Domain Proteins, pubmed-meshheading:20804746-Twist Transcription Factor
pubmed:year
2010
pubmed:articleTitle
Twist1 promotes heart valve cell proliferation and extracellular matrix gene expression during development in vivo and is expressed in human diseased aortic valves.
pubmed:affiliation
The Heart Institute, Cincinnati Children's Medical Center, Cincinnati, OH 45229, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural