Abstract
beta-Catenin/TCF/LEF1 signaling is implicated in cardiac hypertrophy. We demonstrate that knockdown of beta-catenin attenuates phenylephrine (PE)-induced cardiomyocyte hypertrophy and the up-regulation of the fetal gene Anf. We explore the mechanism through which beta-catenin regulates Anf expression and find a consensus binding sequence on the Anf promoter for TCF/LEF1 family members. LEF1 binds directly to the Anf promoter via this sequence, which shows functional significance, and PE stimulation enhances recruitment of beta-catenin onto the Anf promoter. Thus, we document a direct positive role of beta-catenin on PE-induced cardiomyocyte hypertrophy and identify a new target gene for beta-catenin/TCF/LEF1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Atrial Natriuretic Factor / genetics*
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Cardiomegaly / chemically induced
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Cardiomegaly / genetics
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Cardiomegaly / metabolism*
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Gene Expression Regulation*
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Gene Knockdown Techniques
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Lymphoid Enhancer-Binding Factor 1 / metabolism
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Myocytes, Cardiac / drug effects
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Myocytes, Cardiac / metabolism*
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Phenylephrine / pharmacology
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Promoter Regions, Genetic
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Rats
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Rats, Sprague-Dawley
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TCF Transcription Factors / metabolism
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Transcription, Genetic
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Up-Regulation
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beta Catenin / genetics
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beta Catenin / metabolism*
Substances
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Lef1 protein, rat
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Lymphoid Enhancer-Binding Factor 1
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TCF Transcription Factors
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beta Catenin
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Phenylephrine
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Atrial Natriuretic Factor