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dc.contributor.authorKuan, Tang-Chingen_US
dc.contributor.authorYang, Tzu-Huien_US
dc.contributor.authorWen, Cheng-Haoen_US
dc.contributor.authorChen, Mu-Yuanen_US
dc.contributor.authorLee, I-Liangen_US
dc.contributor.authorLin, Chih-Shengen_US
dc.date.accessioned2014-12-08T15:20:49Z-
dc.date.available2014-12-08T15:20:49Z-
dc.date.issued2011-09-01en_US
dc.identifier.issn0196-9781en_US
dc.identifier.urihttp://dx.doi.org/10.1016/j.peptides.2011.08.009en_US
dc.identifier.urihttp://hdl.handle.net/11536/14802-
dc.description.abstractAngiotensin-converting enzyme 2 (ACE2) has been proposed as a potential target for cardioprotection in regulating cardiovascular functions, owing to its key role in the formation of the vasoprotective peptides angiotensin-(1-7) from angiotensin II (Ang II). The regulatory mechanism of ace2 expression, however, remains to be explored. In this study, we investigated the regulatory element within the upstream of ace2. The human ace2 promoter region, from position -2069 to +20, was cloned and a series of upstream deletion mutants were constructed and cloned into a luciferase reporter vector. The reporter luciferase activity was analyzed by transient transfection of the constructs into human cardiofibroblasts (HCFs) and an activating domain was identified in the -516/-481 region. Deletion or reversal of this domain within ace2 resulted in a significant decrease in promoter activity. The nuclear proteins isolated from the HCFs formed a DNA-protein complex with double stranded oligonucleotides of the -516/-481 domain, as detected by electrophoretic mobility shift assay. Site-directed mutagenesis of this region identified a putative protein binding domain and a potential binding site, ATTTGGA, homologous to that of an Ikaros binding domain. This regulatory element was responsible for Ang II stimulation via the Ang II-Ang II type-1 receptor (AT1R) signaling pathway, but was not responsible for pro-inflammatory cytokines TGF-beta 1 and TNF-alpha. Our results suggest that the nucleotide sequences -516/-481 of human ace2 may be a binding domain for an as yet unidentified regulatory factor(s) that regulates ace2 expression and is associated with Ang II stimulation. (C) 2011 Elsevier Inc. All rights reserved.en_US
dc.language.isoen_USen_US
dc.subjectAngiotensin-converting enzyme 2en_US
dc.subjectRegulatory elementen_US
dc.subjectAngiotensin IIen_US
dc.subjectHuman cardiofibroblastsen_US
dc.titleIdentifying the regulatory element for human angiotensin-converting enzyme 2 (ACE2) expression in human cardiofibroblastsen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.peptides.2011.08.009en_US
dc.identifier.journalPEPTIDESen_US
dc.citation.volume32en_US
dc.citation.issue9en_US
dc.citation.spage1832en_US
dc.citation.epage1839en_US
dc.contributor.department生物科技學系zh_TW
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.identifier.wosnumberWOS:000295767400008-
dc.citation.woscount7-
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