Regulation of C-type natriuretic peptide expression

• Published in: Peptides (New York, N.Y. : 1980) Vol. 32; no. 9; pp. 1964 - 1971
• Main Authors: Sellitti, Donald F., Koles, Nancy, Mendonça, Maria C.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-09-2011; Elsevier
• Subjects: Animals; atrial natriuretic peptide; autocrine signaling; binding sites; Biological and medical sciences; bone formation; brain; C-type natriuretic peptide; Cardiovascular Diseases - blood; Cardiovascular Diseases - physiopathology; Cardiovascular System - physiopathology; DNA-binding proteins; Endothelial Cells - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; genes; Genome, Human; guanylate cyclase; Humans; myocardium; Myocytes, Smooth Muscle - metabolism; natriuretic peptide receptors; Natriuretic Peptide, C-Type - blood; Natriuretic Peptide, C-Type - genetics; Natriuretic Peptide, C-Type - metabolism; neurodevelopment; Promoter Regions, Genetic; receptor protein-tyrosine kinase; Regulation; Regulatory Elements, Transcriptional; regulatory proteins; Repressor Proteins - genetics; Repressor Proteins - metabolism; reproduction; RNA, Messenger - metabolism; serine; Signal Transduction; TATA box; threonine; Transcription Factors; transforming growth factor beta; Transforming Growth Factor beta - metabolism; Vertebrates: endocrinology; C-type natriuretic peptide; Gene expression; Regulation; C type natriuretic peptide
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2011.07.013

► Introduction to the family of natriuretic peptides, their receptors, and functions. ► Functional significance of CNP in bone, neural, and cardiovascular tissue. ► Hormonal and pathophysiological determinants of CNP expression. ► Structure of the CNP gene, emphasizing regulatory sequences in promoter. ► Putative CNP transcription factors.
C-type natriuretic peptide (CNP) is a member of the small family of natriuretic peptides that also includes atrial natriuretic peptide (ANP) and brain, or B-type natriuretic peptide (BNP). Unlike them, it performs its major functions in an autocrine or paracrine manner. Those functions, mediated through binding to the membrane guanylyl cyclase natriuretic peptide receptor B (NPR-B), or by signaling through the non-enzyme natriuretic peptide receptor C (NPR-C), include the regulation of endochondral ossification, reproduction, nervous system development, and the maintenance of cardiovascular health. To date, the regulation of CNP gene expression has not received the attention that has been paid to regulation of the ANP and BNP genes. CNP expression in vitro is regulated by TGF-β and receptor tyrosine kinase growth factors in a cell/tissue-specific and sometimes species-specific manner. Expression of CNP in vivo is altered in diseased organs and tissues, including atherosclerotic vessels, and the myocardium of failing hearts. Analysis of the human CNP gene has led to the identification of a number of regulatory sites in the proximal promoter, including a GC-rich region approximately 50 base pairs downstream of the Tata box, and shown to be a binding site for several putative regulatory proteins, including transforming growth factor clone 22 domain 1 (TSC22D1) and a serine threonine kinase (STK16). The purpose of this review is to summarize the current literature on the regulation of CNP expression, emphasizing in particular the putative regulatory elements in the CNP gene and the potential DNA-binding proteins that associate with them.