Molecular structure and transcriptional regulation by nuclear factor-κB of the mouse kinin B1 receptor gene

Vanessa Merino, José A. Silva, Ronaldo C. Araújo, Maria C W Avellar, Jean L. Bascands, Joost P. Schanstra, Antonio C M Paiva, Michael Bader, João B. Pesquero

Research output: Contribution to journalArticle

Abstract

Kinins are important mediators in cardiovascular homeostasis, inflammation, and nociception. Two kinin receptors have been described, B1 and B2. The B1 receptor is normally absent in healthy tissues, but is highly induced under pathological conditions. To understand the molecular mechanism of B1 receptor up-regulation, we determined the mouse B1 receptor gene structure, isolated and characterized the promoter region and studied its transcriptional regulation. The mouse B1 receptor gene contains two exons (with the entire coding region located in the second exon) and a TATA-less promoter with multiple transcription start sites. A 7.7-kbp portion of the 5′-flanking region was examined for promoter activity in vascular smooth muscle cells (VSMCs). A minimal 92-bp fragment, located immediately upstream of the transcription start region, exerted basal and lipopolysaccharide (LPS)-inducible transcription activity in the sense and antisense orientation, and was thereby identified as an enhancer element. Nuclear extracts from VSMCs showed basal and LPS-inducible binding activity of nuclear factor (NF)-κB at this sequence. B1 receptor transcription activation in response to LPS was abolished by cotransfection with IκBαΔN, an NF-κB repressor. In summary, our results reveal the structure of the mouse B1 receptor gene and the involvement of NF-κB in the inducible mouse kinin B1 receptor expression under pathological conditions.

Original languageEnglish (US)
Pages (from-to)515-522
Number of pages8
JournalBiological Chemistry
Volume386
Issue number6
DOIs
StatePublished - 2005
Externally publishedYes

Fingerprint

Kinins
Transcription
Molecular Structure
Molecular structure
Lipopolysaccharides
Genes
Muscle
Exons
Vascular Smooth Muscle
Smooth Muscle Myocytes
5' Flanking Region
Transcription Initiation Site
Genetic Promoter Regions
Nociception
Chemical activation
Cells
Tissue
Transcriptional Activation
Homeostasis
Up-Regulation

Keywords

  • Enhancer
  • Lipopolysaccharide (LPS)
  • Mouse kinin B receptor gene
  • Multiple transcription start sites
  • Nuclear factor-κB (NF-κB)
  • Promoter
  • VSMC

ASJC Scopus subject areas

  • Biochemistry

Cite this

Merino, V., Silva, J. A., Araújo, R. C., Avellar, M. C. W., Bascands, J. L., Schanstra, J. P., ... Pesquero, J. B. (2005). Molecular structure and transcriptional regulation by nuclear factor-κB of the mouse kinin B1 receptor gene. Biological Chemistry, 386(6), 515-522. https://doi.org/10.1515/BC.2005.061

Molecular structure and transcriptional regulation by nuclear factor-κB of the mouse kinin B1 receptor gene. / Merino, Vanessa; Silva, José A.; Araújo, Ronaldo C.; Avellar, Maria C W; Bascands, Jean L.; Schanstra, Joost P.; Paiva, Antonio C M; Bader, Michael; Pesquero, João B.

In: Biological Chemistry, Vol. 386, No. 6, 2005, p. 515-522.

Research output: Contribution to journalArticle

Merino, V, Silva, JA, Araújo, RC, Avellar, MCW, Bascands, JL, Schanstra, JP, Paiva, ACM, Bader, M & Pesquero, JB 2005, 'Molecular structure and transcriptional regulation by nuclear factor-κB of the mouse kinin B1 receptor gene', Biological Chemistry, vol. 386, no. 6, pp. 515-522. https://doi.org/10.1515/BC.2005.061
Merino, Vanessa ; Silva, José A. ; Araújo, Ronaldo C. ; Avellar, Maria C W ; Bascands, Jean L. ; Schanstra, Joost P. ; Paiva, Antonio C M ; Bader, Michael ; Pesquero, João B. / Molecular structure and transcriptional regulation by nuclear factor-κB of the mouse kinin B1 receptor gene. In: Biological Chemistry. 2005 ; Vol. 386, No. 6. pp. 515-522.
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