Up-regulation of natriuretic peptides in the ventricle of Csx/Nkx2-5 transgenic mice - PubMed

Affiliations

• PMID: 10772952
• DOI: 10.1006/bbrc.2000.2561

Up-regulation of natriuretic peptides in the ventricle of Csx/Nkx2-5 transgenic mice

E Takimoto et al. Biochem Biophys Res Commun. 2000.

Abstract

A cardiac homeobox-containing gene Csx/Nkx2-5, which is essential for cardiac development, is abundantly expressed in the adult heart as well as in the heart primordia. Targeted disruption of this gene results in embryonic lethality due to abnormal heart morphogenesis. To elucidate the role of Csx/Nkx2-5 in the adult heart, we generated transgenic mice which overexpress human Csx/Nkx2-5. The transgene was expressed abundantly in the heart and the skeletal muscle. mRNA levels of several cardiac genes including natriuretic peptides, CARP, MLC2v, and endogenous Csx/Nkx2-5 were increased in the ventricle of the transgenic mice. Electron microscopic analysis revealed that the ventricular myocardium of the transgenic mice had many secretory granules, which disappeared after administration of vasopressin. These results suggest that Csx/Nkx2-5 regulates many cardiac genes and induces formation of secretory granules in the adult ventricle.

Similar articles

• CARP, a cardiac ankyrin repeat protein, is downstream in the Nkx2-5 homeobox gene pathway.

  Zou Y, Evans S, Chen J, Kuo HC, Harvey RP, Chien KR. Zou Y, et al. Development. 1997 Feb;124(4):793-804. doi: 10.1242/dev.124.4.793. Development. 1997. PMID: 9043061

• Progressive atrioventricular conduction defects and heart failure in mice expressing a mutant Csx/Nkx2.5 homeoprotein.

  Kasahara H, Wakimoto H, Liu M, Maguire CT, Converso KL, Shioi T, Huang WY, Manning WJ, Paul D, Lawitts J, Berul CI, Izumo S. Kasahara H, et al. J Clin Invest. 2001 Jul;108(2):189-201. doi: 10.1172/JCI12694. J Clin Invest. 2001. PMID: 11457872 Free PMC article.

• The cardiac tissue-restricted homeobox protein Csx/Nkx2.5 physically associates with the zinc finger protein GATA4 and cooperatively activates atrial natriuretic factor gene expression.

  Lee Y, Shioi T, Kasahara H, Jobe SM, Wiese RJ, Markham BE, Izumo S. Lee Y, et al. Mol Cell Biol. 1998 Jun;18(6):3120-9. doi: 10.1128/MCB.18.6.3120. Mol Cell Biol. 1998. PMID: 9584153 Free PMC article.

• Cardiac transcription factor Csx/Nkx2-5: Its role in cardiac development and diseases.

  Akazawa H, Komuro I. Akazawa H, et al. Pharmacol Ther. 2005 Aug;107(2):252-68. doi: 10.1016/j.pharmthera.2005.03.005. Pharmacol Ther. 2005. PMID: 15925411 Review.

• Molecular mechanism of cardiac hypertrophy and development.

  Komuro I. Komuro I. Jpn Circ J. 2001 May;65(5):353-8. doi: 10.1253/jcj.65.353. Jpn Circ J. 2001. PMID: 11348034 Review.

Cited by

• Re-employment of developmental transcription factors in adult heart disease.

  Oka T, Xu J, Molkentin JD. Oka T, et al. Semin Cell Dev Biol. 2007 Feb;18(1):117-31. doi: 10.1016/j.semcdb.2006.11.012. Epub 2006 Nov 24. Semin Cell Dev Biol. 2007. PMID: 17161634 Free PMC article. Review.

• The lncRNA Sweetheart regulates compensatory cardiac hypertrophy after myocardial injury in murine males.

  Rogala S, Ali T, Melissari MT, Währisch S, Schuster P, Sarre A, Emídio RC, Boettger T, Rogg EM, Kaur J, Krishnan J, Dumbović G, Dimmeler S, Ounzain S, Pedrazzini T, Herrmann BG, Grote P. Rogala S, et al. Nat Commun. 2023 Nov 2;14(1):7024. doi: 10.1038/s41467-023-42760-y. Nat Commun. 2023. PMID: 37919291 Free PMC article.

• The Polycomb-group gene Rae28 sustains Nkx2.5/Csx expression and is essential for cardiac morphogenesis.

  Shirai M, Osugi T, Koga H, Kaji Y, Takimoto E, Komuro I, Hara J, Miwa T, Yamauchi-Takihara K, Takihara Y. Shirai M, et al. J Clin Invest. 2002 Jul;110(2):177-84. doi: 10.1172/JCI14839. J Clin Invest. 2002. PMID: 12122109 Free PMC article.

• An early requirement for nkx2.5 ensures the first and second heart field ventricular identity and cardiac function into adulthood.

  George V, Colombo S, Targoff KL. George V, et al. Dev Biol. 2015 Apr 1;400(1):10-22. doi: 10.1016/j.ydbio.2014.12.019. Epub 2014 Dec 20. Dev Biol. 2015. PMID: 25536398 Free PMC article.

• Cardiovascular genomics: a current overview of in vivo and in vitro studies.

  Mariappan D, Winkler J, Hescheler J, Sachinidis A. Mariappan D, et al. Stem Cell Rev. 2006;2(1):59-66. doi: 10.1007/s12015-006-0010-2. Stem Cell Rev. 2006. PMID: 17142888 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)

• Research Materials

  • NCI CPTC Antibody Characterization Program