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首页> 外文期刊>Physiological Research >Hepcidin Downregulation by Repeated Bleeding Is Not Mediated by Soluble Hemojuvelin
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Hepcidin Downregulation by Repeated Bleeding Is Not Mediated by Soluble Hemojuvelin

机译：反复出血引起的铁调素下调不是由可溶性血丝素介导的

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Hepcidin is a key regulator of iron homeostasis, while hemojuvelin is an important component of the hepcidin regulation pathway. It has been recently proposed that soluble hemojuvelin, produced from hemojuvelin by the protease furin, decreases hepcidin expression. The aim of the presented study was to examine the downregulation of hepcidin by chronic bleeding in hemojuvelin-mutant mice. Male mice with targeted disruption of the hemojuvelin gene (Hjv-/- mice) and wild-type littermates were maintained on an iron-deficient diet and subjected to weekly phlebotomies for 7 weeks. Gene expression was examined by real-time PCR. In wild type mice, repeated bleeding decreased hepcidin mRNA by two orders of magnitude. In Hjv-/- mice, basal hepcidin expression was low; however, repeated bleeding also decreased hepcidin mRNA content by an order of magnitude. Phlebotomies reduced hepatic iron overload in Hjv-/- mice by 80 %. Liver and muscle furin mRNA content was not significantly changed. No effect on hepatic Tmprss6 mRNA content was observed. Results from the study indicate that soluble hemojuvelin is not the sole factor responsible for hepcidin downregulation. In addition, the presented data suggest that, under in vivo conditions, tissue hypoxia does not transcriptionally regulate the activity of furin or TMPRSS6 proteases.
机译：铁调素是铁稳态的关键调节剂，而血juvelin是铁调素调节途径的重要组成部分。最近已经提出，由蛋白酶弗林蛋白酶从血枣素产生的可溶性血枣素降低了铁调素的表达。提出的研究的目的是检查血红蛋白突变小鼠中慢性出血对铁调素的下调。靶向破坏血juvelin基因的雄性小鼠（Hjv-/-小鼠）和野生型同窝仔动物维持铁缺乏饮食，每周进行静脉切开术7周。通过实时PCR检查基因表达。在野生型小鼠中，反复出血使铁调素mRNA降低了两个数量级。在Hjv-/-小鼠中，基础hepcidin表达低;然而，反复出血也使铁调素mRNA含量降低了一个数量级。静脉切开术可将Hjv-/-小鼠的肝铁超负荷降低80％。肝和肌肉弗林蛋白酶mRNA含量没有明显改变。没有观察到对肝脏Tmprss6 mRNA含量的影响。该研究结果表明，可溶性血枣素不是引起铁调素下调的唯一因素。此外，提出的数据表明，在体内条件下，组织缺氧不能转录调节弗林蛋白酶或TMPRSS6蛋白酶的活性。

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