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Vanessa F. 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

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

Keywords: enhancer, lipopolysaccharide (LPS), mouse kinin B1 receptor gene, multiple transcription start sites, nuclear factor-?B (NF-?B), promoter, VSMC

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)-?B at this sequence. B1 receptor transcription activation in response to LPS was abolished by cotransfection with I?B??N, an NF-?B repressor. In summary, our results reveal the structure of the mouse B1 receptor gene and the involvement of NF-?B in the inducible mouse kinin B1 receptor expression under pathological conditions.

Biological Chemistry, Walter de Gruyter

Print ISSN: 1431-6730
Volume: 386, 06/2005
Pages: 515 - 522

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