Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-1-17
pubmed:abstractText
Several genes, including fibroblast growth factor 2 (FGF2), are up-regulated in the hypertrophic heart. However, the molecular mechanisms responsible for the angiotensin II (Ang II)-induced activation of FGF2 in cardiomyocyte hypertrophy are largely unknown. The purpose of this study was to determine the signaling cascades underlying the Ang II-induced transcriptional activation of FGF2 in neonatal rat cardiomyocytes. Real-time quantitative RT-PCR and Western blot showed that Ang II upregulates FGF2 expression and that these effects were attenuated by U0126 or SB203580, but not by SP600125. Deletion analyses revealed that the region between -845 and -666 is essential for Ang II-induced FGF2 promoter activity. The existence of an atypical GATA4-binding motif, located at position -752, was identified using electrophoretic mobility shift assay (EMSA). Using both EMSA and chromatin immunoprecipitation (ChIP) analyses, we also showed that Ang II increases binding of GATA4 to DNA, and that this effect is attenuated in the presence of U0126 or SB203580, but not in the presence of SP600125. GATA4 siRNA significantly reduced Ang II-induced FGF2 mRNA levels. Together, these results indicate that binding of GATA4 to DNA is increased by Ang II via extracellular signal-regulated protein kinase 1/2 (ERK 1/2) and p38 kinase, which increases FGF2 gene expression in neonatal rat cardiomyocytes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1873-2968
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
518-25
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Mitogen-activated protein kinases ERK 1/2- and p38-GATA4 pathways mediate the Ang II-induced activation of FGF2 gene in neonatal rat cardiomyocytes.
pubmed:affiliation
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't