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

Abstract:

: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.

journal_name

Peptides

journal_title

Peptides

authors

Kumar P,Arise KK,Pandey KN

doi

10.1016/j.peptides.2006.01.004

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

1762-9

issue

7

eissn

0196-9781

issn

1873-5169

pii

S0196-9781(06)00034-9

journal_volume

27

pub_type

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