Transcriptional regulation of guanylyl cyclase/natriuretic peptide receptor-A gene

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• 作者：Prerna Kumar ; Kiran K. Arise and Kailash N. Pandey
• 关键词：Natriuretic peptides ; Npr1 promoter ; Gene transcription ; Ets-1 ; Mesangial cells
• 刊名：Peptides
• 出版年：2006
• 出版时间：July 2006
• 年：2006
• 卷：27
• 期：7
• 页码：1762-1769
• 全文大小：367 K

文摘

Activation of natriuretic peptide receptor-A (NPRA) produces the second messenger cGMP, which plays a pivotal role in maintaining blood pressure and cardiovascular homeostasis. In the present study, we have examined the role of trans-acting factor Ets-1 in transcriptional regulation of Npr1 gene (coding for NPRA). Using deletional analysis of the Npr1 promoter, we have defined a 400 base pair (bp) region as the core promoter, which contains consensus binding sites for transcription factors including: Ets-1, Lyf-1, and GATA-1/2. Overexpression of Ets-1 in mouse mesangial cells (MMCs) enhanced Npr1 gene transcription by 12-fold. However, overexpression of GATA-1 or Lyf-1 repressed Npr1 basal promoter activity by 50 % and 80 % , respectively. The constructs having a mutant Ets-1 binding site or lacking this site failed to respond to Ets-1 activation of Npr1 gene transcription. Collectively, the present results demonstrate that Ets-1 greatly stimulates Npr1 gene promoter activity, implicating its critical role in the regulation and function of NPRA at the molecular level.