1998年2月
Transcriptional regulation of human adrenomedullin gene in vascular endothelial cells
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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- ,
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- 巻
- 243
- 号
- 2
- 開始ページ
- 463
- 終了ページ
- 470
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1006/bbrc.1998.8110
- 出版者・発行元
- ACADEMIC PRESS INC
Adrenomedullin (AM) is a recently identified vasodilator peptide produced in cardiovascular organs such as the heart, vascular wall, kidney and lung. Because plasma levels of AM are not different between various portions of the cardiovascular system, vascular cells are supposed to be the main source of circulating AM. To elucidate the regulatory mechanism of human AM gene expression, functional elements of 5'-flanking region of AM gene were studied in human aortic endothelial cells (HAEC). Northern blot analysis revealed considerable AM mRNA expression in cultured HAEC, and 2 transcription start sites were recognized at 21 and 25 bp downstream from the TATA box. The 1534 bp 5'-flanking region DNA inserted in the luciferase vector showed significant promoter activity when transfected into HAEC using liposome. Serial deletion of the inserted 5'-flanking region DNA length resulted in reduction in promoter activity by 41% between 110 and 90 bp and further reduction by 42% between 66 and 29 bp. The 19 bp DNA fragment without TATA box had almost no promoter activity. Gel shift assay revealed presence of HAEC nuclear proteins specifically bound to nuclear factor for interleukin-6 expression (NF-IL6) consensus sequence existing from -85 to -93 bp of the AM gene 5'-flanking region and activator protein 2 (AP-2) consensus sequence clustered from -33 to -68 bp. Furthermore, mutation of NF-IL6 consensus sequence in the 5'-flanking region resulted in 42% reduction in the expression of luciferase activity. These findings suggest that NF-IL6 and AP-2 sites in the promoter region are the functional elements in the transcriptional regulation of human AM gene in vascular endothelial cells. (C) 1998 Academic Press.
- リンク情報
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- DOI
- https://doi.org/10.1006/bbrc.1998.8110
- CiNii Articles
- http://ci.nii.ac.jp/naid/30017798089
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/9480831
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000072130300023&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1006/bbrc.1998.8110
- ISSN : 0006-291X
- CiNii Articles ID : 30017798089
- PubMed ID : 9480831
- Web of Science ID : WOS:000072130300023