Abstract

The atrial natriuretic peptide is a cardiac hormone which plays an important role in regulation of cardiovascular and renal function. ANP is produced predominately in the cardiac atria while relatively small amounts are also found in the ventricule which can be activated to a very high level under certain developmental and pathophysiological conditions. The ANP gene is regulated by a variety of hormones and neuro transmitters including glucocorticoids, vitamin D, thyroid hormone and endothelin. The investigators propose to identify the regulatory factors which control expression of the ANP gene and decipher the mechanism underlying the negative regulation of this gene by the liganded vitamin D receptor. They will attempt to dissect the mechanism through which two regulatory elements, the AP-1 sensitive thyroid hormone responsive element (TRE) and the serum response element control ANP gene transcription. They will also attempt to develop a transcription system capable of initiating expression of ANP gene in vitro. Taken together these experiments should provide a definitive picture of the molecular controls which operate to govern tissue specific and regulated transcription of ANP gene.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL035753-13
Application #
2702173
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1985-09-30
Project End
1999-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
13
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Xiang, Wei; Kong, Juan; Chen, Songcang et al. (2005) Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. Am J Physiol Endocrinol Metab 288:E125-32
Chen, Songcang; Nakamura, Karl; Gardner, David G (2005) 1,25-dihydroxyvitamin D inhibits human ANP gene promoter activity. Regul Pept 128:197-202
Anderson, Hope D I; Wang, Feng; Gardner, David G (2004) Role of the epidermal growth factor receptor in signaling strain-dependent activation of the brain natriuretic peptide gene. J Biol Chem 279:9287-97
Liang, Faquan; Wang, Feng; Zhang, Sumei et al. (2003) Peroxisome proliferator activated receptor (PPAR)alpha agonists inhibit hypertrophy of neonatal rat cardiac myocytes. Endocrinology 144:4187-94
Gardner, David G (2003) Natriuretic peptides: markers or modulators of cardiac hypertrophy? Trends Endocrinol Metab 14:411-6
Liang, Faquan; Webb, Paul; Marimuthu, Adhirai et al. (2003) Triiodothyronine increases brain natriuretic peptide (BNP) gene transcription and amplifies endothelin-dependent BNP gene transcription and hypertrophy in neonatal rat ventricular myocytes. J Biol Chem 278:15073-83
Ilic, Dusko; Kovacic, Branka; McDonagh, Susan et al. (2003) Focal adhesion kinase is required for blood vessel morphogenesis. Circ Res 92:300-7
Liang, F; Kovacic-Milivojevic, B; Chen, S et al. (2001) Signaling mechanisms underlying strain-dependent brain natriuretic peptide gene transcription. Can J Physiol Pharmacol 79:640-5
Kovacic-Milivojevic, B; Roediger, F; Almeida, E A et al. (2001) Focal adhesion kinase and p130Cas mediate both sarcomeric organization and activation of genes associated with cardiac myocyte hypertrophy. Mol Biol Cell 12:2290-307
Ni, X P; Safai, M; Gardner, D G et al. (2001) Increased cGMP phosphodiesterase activity mediates renal resistance to ANP in rats with bile duct ligation. Kidney Int 59:1264-73

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