ZFIN ID: ZDB-PUB-070330-16
Bone morphogenetic protein-2 acts upstream of myocyte-specific enhancer factor 2a to control embryonic cardiac contractility
Wang, Y.X., Qian, L.X., Liu, D., Yao, L.L., Jiang, Q., Yu, Z., Gui, Y.H., Zhong, T.P., and Song, H.Y.
Date: 2007
Source: Cardiovascular research   74(2): 290-303 (Journal)
Registered Authors: Jiang, Qiu, Qian, Linxi, Wang, Yuexiang, Zhong, Tao P.
Keywords: Developmental biology, Contractile function, Heart failure, Cardiomyopathy
MeSH Terms:
  • Animals
  • Animals, Newborn
  • Base Sequence
  • Blotting, Western
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins/analysis
  • Bone Morphogenetic Proteins/genetics
  • Bone Morphogenetic Proteins/metabolism*
  • Carrier Proteins/pharmacology
  • Cells, Cultured
  • Gene Expression Regulation/drug effects
  • Genetic Engineering
  • Heart/embryology
  • Humans
  • MADS Domain Proteins/analysis
  • MADS Domain Proteins/genetics
  • MADS Domain Proteins/metabolism*
  • MEF2 Transcription Factors
  • Molecular Sequence Data
  • Myocardial Contraction/physiology*
  • Myocytes, Cardiac/physiology*
  • Myogenic Regulatory Factors/analysis
  • Myogenic Regulatory Factors/genetics
  • Myogenic Regulatory Factors/metabolism*
  • Organisms, Genetically Modified
  • RNA Interference
  • RNA, Small Interfering/administration & dosage
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction/physiology*
  • Transforming Growth Factor beta/analysis
  • Transforming Growth Factor beta/genetics
  • Transforming Growth Factor beta/metabolism*
  • Zebrafish/embryology
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
PubMed: 17367767 Full text @ Cardiovasc. Res.
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ABSTRACT
OBJECTIVE: Cardiac contractility is regulated tightly as an extrinsic and intrinsic homeostatic mechanism to the heart. The molecular basis of the intrinsic system is largely unknown. Here, we test the hypothesis that bone morphogenetic protein-2 (BMP-2) mediates embryonic cardiac contractility upstream of myocyte-specific enhancer factor 2A (MEF2A). METHODS: The BMP-2 and MEF2A expression pattern was analyzed by RT-PCR, Western blotting, whole-mount in situ hybridization, and an in vivo transgenic approach. The cardiac phenotype of BMP-2 and MEF2A knock-down zebrafish embryos was analysed. Cardiac contractions were recorded with a video camera. Myofibrillar organization was observed with transmission electron microscopy. Gene expression profiles were performed by quantitative real-time PCR analysis. RESULTS: We demonstrate that BMP-2 and MEF2A are co-expressed in embryonic and neonatal cardiac myocytes. Furthermore, we provide evidence that BMP-2 is required for cardiac contractility in vitro and in vivo and that MEF2A expression can be activated by BMP-2 signaling in neonatal cardiomyocytes. BMP-2 is involved in the assembly of the cardiac contractile apparatus. Finally, we find that exogenous MEF2A is sufficient to rescue ventricular contractility defects in the absence of BMP-2 function. CONCLUSIONS: In all, these observations indicate that BMP-2 and MEF2A are key components of a pathway that controls the cardiac ventricular contractility and suggest that the BMP2-MEF2A pathway can offer new opportunities for the treatment of heart failure.
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