期刊
CELL BIOLOGY INTERNATIONAL
卷 35, 期 1, 页码 1-8出版社
WILEY
DOI: 10.1042/CBI20100290
关键词
a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS); hypoxia; metalloproteinase; promoter
类别
资金
- Japan Society for the Promotion of Science [20390399]
- Grants-in-Aid for Scientific Research [23390366, 10F00118] Funding Source: KAKEN
ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an early immediate gene. We have previously reported that ADAMTS1 was strongly induced by hypoxia. In this study, we investigated whether ADAMTS1 promoter-driven reporter signal is detectable by acute hypoxia. We constructed the GFP (green fluorescent protein) expression vector [AHR (acute hypoxia-response sequence)-GFP] under the control of ADAMTS1 promoter and compared it with the constitutive GFP-expressing vector under the control of CMV (cytomegalovirus promoter-OFF). We transduced AHR-GFP and examined whether OFF signals can be detected under the acute hypoxia. When the human umbilical vein [HUVEC (human umbilical vein endothelial cells)] was transduced under normoxia, there were few GFP signals, while CMV-GFP showed considerable GFP signals. When HUVEC was stimulated with hypoxia, OFF signals from AHR-GFP gene were induced under hypoxic conditions. Notably, the OFF signals peaked at 3 h under hypoxia. In ischaemic hind limb model, transduced AHR-GFP showed hypoxic induction of GFP signals. In summary, we have demonstrated that the AHR system induced the reporter gene expression by acute hypoxia, and its induction is transient. This is the first report showing the unique acute hypoxia-activated gene expression system.
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