title: Matriptase-2 (TMPRSS6) is directly up-regulated by hypoxia inducible factor-1: identification of a hypoxia-responsive element in the TMPRSS6 promoter region.
abstract: 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-1α-dependent induction of TMPRSS6 expression. The action of HIF-1α on TMPRSS6 promoter activity reveals a new regulative element for the suppression of hepcidin synthesis.
authors.affiliation: Pharmaceutical Institute, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Maurer
authors.forename: Michael
authors.initials: M
authors.lastname: Gütschow
authors.forename: Marit
authors.initials: M
authors.lastname: Stirnberg
mesh_terms: D015687:Cell Hypoxia / Q000235:genetics; D002460:Cell Line; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D000090463:Iron Deficiencies; D008565:Membrane Proteins / Q000235:genetics*; D020218:Response Elements / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human