© 2002 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Fibronectin signaling stimulates BNP gene transcription by inhibiting neuron-restrictive silencer element-dependent repression
aDepartment of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
bDepartment of Molecular Genetic Research, National Institute for Longevity Science, Obu, Aichi 474-8522, Japan
cCREST, Science and Technology corporation of Japan (JST), Obu, Aichi 474-8522 Japan
* Corresponding author. Tel.: +81-75-751-3180; fax: +81-75-751-4351 yssaito{at}kuhp.kyoto-u.ac.jp
Objective: Brain natriuretic peptide (BNP) is a cardiac hormone mainly synthesized in ventricles and its expression is markedly increased in ventricular hypertrophy that involves the accumulation of extracellular matrix proteins, such as fibronectin (Fn). We recently reported that Fn signaling stimulated BNP secretion accompanied by hypertrophic responses in vitro. Methods: To elucidate the regulatory mechanism for BNP gene transcription, we examined cis-acting elements downstream of Fn signaling in rat ventricular myocytes transfected with either the –1812 human BNP-luciferase reporter gene (–1812hBNP/Luc) or one of several truncated forms. Results: A strong cis-repressor element was identified between –552 and –522 in myocytes plated on uncoated dishes. This region contains a neuron-restrictive silencer element (NRSE)-like element (NRSEBNP) that is 90% homologous with the NRSE consensus sequence. Neuron-restrictive silencer factor (NRSF) is known to bind to NRSE and to silence transcription of genes containing NRSE. Deletion of NRSEBNP and dominant negative NRSF markedly increased the reporter activity in transfected cells, suggesting that the NRSE/NRSF system silences basal BNP gene transcription. When myocytes were cultured on Fn-coated dishes, the reporter activity of –1812hBNP/Luc was increased by 
600% compared with that on uncoated dishes. Interestingly, truncation from –552 to –522 reduced the Fn-inducible reporter activity. Moreover, deletion of NRSEBNP and dominant negative NRSF also inhibited the Fn-inducible reporter activity. Electrophoretic mobility shift assays showed that Fn signaling inhibited the binding activity of NRSF to NRSEBNP. Conclusion: These results suggest that Fn-induced BNP up-regulation in rat ventricular myocytes is due to inhibition of NRSEBNP-dependent repression of BNP gene transcription.
KEYWORDS Extracellular matrix; Gene expression; Hypertrophy; Myocytes; Natriuretic peptide
1 Present address: The UBC McDonald Research Laboratories/The iCAPTURE Centre, Department of Pathology and Laboratory Medicine, St. Paul's Hospital/Providence Health Care, University of British Columbia, Vancouver, BC, Canada.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Nakagawa, K. Kuwahara, G. Takemura, M. Akao, M. Kato, Y. Arai, M. Takano, M. Harada, M. Murakami, M. Nakanishi, et al. p300 Plays a Critical Role in Maintaining Cardiac Mitochondrial Function and Cell Survival in Postnatal Hearts Circ. Res., October 9, 2009; 105(8): 746 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Somekawa, K. Imagawa, N. Naya, Y. Takemoto, K. Onoue, S. Okayama, Y. Takeda, H. Kawata, M. Horii, T. Nakajima, et al. Regulation of Aldosterone and Cortisol Production by the Transcriptional Repressor Neuron Restrictive Silencer Factor Endocrinology, July 1, 2009; 150(7): 3110 - 3117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Otto, S. R. McCorkle, J. Hover, C. Conaco, J.-J. Han, S. Impey, G. S. Yochum, J. J. Dunn, R. H. Goodman, and G. Mandel A New Binding Motif for the Transcriptional Repressor REST Uncovers Large Gene Networks Devoted to Neuronal Functions J. Neurosci., June 20, 2007; 27(25): 6729 - 6739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Bingham, L. Ooi, L. Kozera, E. White, and I. C. Wood The Repressor Element 1-Silencing Transcription Factor Regulates Heart-Specific Gene Expression Using Multiple Chromatin-Modifying Complexes Mol. Cell. Biol., June 1, 2007; 27(11): 4082 - 4092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Gardner, S. Chen, D. J. Glenn, and C. L. Grigsby Molecular Biology of the Natriuretic Peptide System: Implications for Physiology and Hypertension Hypertension, March 1, 2007; 49(3): 419 - 426. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Simo, L. Pujadas, M. F. Segura, A. L. Torre, J. A. Del Rio, J. M. Urena, J. X. Comella, and E. Soriano Reelin Induces the Detachment of Postnatal Subventricular Zone Cells and the Expression of the Egr-1 through Erk1/2 Activation Cereb Cortex, February 1, 2007; 17(2): 294 - 303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Houweling, M. M. van Borren, A. F.M. Moorman, and V. M. Christoffels Expression and regulation of the atrial natriuretic factor encoding gene Nppa during development and disease Cardiovasc Res, September 1, 2005; 67(4): 583 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Chen, X. N. Huang, A. F. R. Stewart, and J. L. Sepulveda Gene expression changes associated with fibronectin-induced cardiac myocyte hypertrophy Physiol Genomics, August 11, 2004; 18(3): 273 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. W. Bruce, I. J. Donaldson, I. C. Wood, S. A. Yerbury, M. I. Sadowski, M. Chapman, B. Gottgens, and N. J. Buckley Genome-wide analysis of repressor element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) target genes PNAS, July 13, 2004; 101(28): 10458 - 10463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ogawa, W. M. Elliott, F. Hughes, T. J. Eichholtz, J. C. Hogg, and S. Hayashi Latent adenoviral infection induces production of growth factors relevant to airway remodeling in COPD Am J Physiol Lung Cell Mol Physiol, January 1, 2004; 286(1): L189 - L197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Liang, F. Wang, S. Zhang, and D. G. Gardner Peroxisome Proliferator Activated Receptor (PPAR){alpha} Agonists Inhibit Hypertrophy of Neonatal Rat Cardiac Myocytes Endocrinology, September 1, 2003; 144(9): 4187 - 4194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Mason and N. A. Wahab Extracellular Matrix Metabolism in Diabetic Nephropathy J. Am. Soc. Nephrol., May 1, 2003; 14(5): 1358 - 1373. [Abstract] [Full Text] [PDF]
|
|