期刊
BIOLOGICAL CHEMISTRY
卷 393, 期 6, 页码 535-540出版社
WALTER DE GRUYTER GMBH
DOI: 10.1515/hsz-2011-0221
关键词
hepcidin; iron deficiency; reporter gene assay; transcriptional regulation; type II transmembrane serine protease
资金
- Bayer HealthCare Pharmaceuticals, Wuppertal, Germany
The type II transmembrane serine protease matriptase-2 (TMPRSS6) down-regulates the expression of hepcidin, the main regulator of systemic iron homeostasis, and increases in this way iron plasma levels. Matriptase-2 is up-regulated under hypoxic conditions, providing a new link between hypoxia signaling and iron homeostasis. In this study, we have characterized the TMPRSS6 promoter region and identified a functional hypoxia-responsive element (HRE). Mutations of the hypoxia inducible factor (HIF)-binding site located within the HRE abrogate HIF-1 alpha-dependent induction of TMPRSS6 expression. The action of HIF-1 alpha on TMPRSS6 promoter activity reveals a new regulative element for the suppression of hepcidin synthesis.
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