Function of hemojuvelin in the heart and skeletal muscles

血幼素在心脏和骨骼肌中的功能

• 批准号: RGPIN-2017-05406
• 负责人: Pantopoulos, Konstantinos
• 金额: $ 1.89万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629566
• 关键词: Function; hemojuvelin; heart; skeletal; muscles

Mammalian dietary iron absorption and body iron traffic are controlled by hepcidin, a liver-derived peptide hormone. Hepcidin binds to the iron exporter ferroportin in target cells and promotes its degradation, thereby inhibiting iron flux into the bloodstream. The expression of hepcidin requires hemojuvelin (Hjv), a bone morphogenetic protein (BMP) co-receptor. Hjv operates by enhancing iron-dependent BMP/SMAD signaling to hepcidin in the liver, the major site of hepcidin production. Liver-specific disruption of either hepcidin or Hjv leads to severe iron overload. Both hepcidin and Hjv are also expressed in other tissues, where they may exert localized functions. Hjv is highly abundant in the heart and skeletal muscles. By generating liver- and muscle-specific Hjv-/- mice, we demonstrated that only liver Hjv regulates systemic iron homeostasis.

哺乳动物膳食铁吸收和体内铁运输受肝源性肽激素铁调素控制。铁调素与靶细胞中的铁输出蛋白ferroportin结合并促进其降解，从而抑制铁流入血流。铁调素的表达需要血幼素（hemojuvelin，HSP 70），一种骨形态发生蛋白（BMP）共受体。阻碍通过增强铁依赖性BMP/SMAD信号传导至肝中的铁调素（铁调素产生的主要部位）来起作用。肝特异性铁调素或铁调素的破坏导致严重的铁过载。hepcidin和hepcidin也在其他组织中表达，在那里它们可以发挥局部功能。心脏和骨骼肌中有大量的阻碍物。通过产生肝脏和肌肉特异性HSP 70-/-小鼠，我们证明了只有肝脏HSP 70调节全身铁稳态。