血红素结合蛋白在小鼠中转铁蛋白依赖性和非依赖性铁调素表达中是必需的。
Hemojuvelin is essential for transferrin-dependent and transferrin-independent hepcidin expression in mice.
机构信息
Department of Pathology, Children's Hospital, Boston, MA 02115, USA.
出版信息
Haematologica. 2012 Feb;97(2):189-92. doi: 10.3324/haematol.2011.054031. Epub 2011 Oct 11.
Abstract
Here we investigate the regulation of hepcidin, a hormone that inhibits dietary iron absorption and macrophage iron recycling, by the serum iron-binding protein transferrin. Mice deficient in transferrin (Tf(hpx/hpx)) and hemojuvelin (Hjv(-/-)), a gene mutated in juvenile hemochromatosis, a disease of hepcidin deficiency and iron overload, were generated. While Tf(hpx/hpx) Hjv(+/+) and Tf(hpx/hpx) Hjv(-/-) phenotypes did not differ markedly, transferrin treatment and RBC transfusions robustly increased hepcidin levels in Tf(hpx/hpx) Hjv(+/+) but not Tf(hpx/hpx) Hjv(-/-)mice. These results suggest that, while hemojuvelin is not essential for the establishment or maintenance of hepcidin deficiency in transferrin-deficient mice, hemojuvelin is essential for transferrin-dependent and transferrin-independent hepcidin expression in conditions of iron overload.
摘要
在这里，我们研究了转铁蛋白（一种抑制膳食铁吸收和巨噬细胞铁再循环的激素）对铁调素的调节作用。我们生成了转铁蛋白（Tf）缺失（Tf(hpx/hpx))和幼年期血色病（一种铁调素缺乏和铁过载的疾病）突变基因血红蛋白（Hjv）缺失（Hjv(-/-))的小鼠。虽然 Tf(hpx/hpx) Hjv(+/+)和 Tf(hpx/hpx) Hjv(-/-)表型没有明显差异，但转铁蛋白治疗和红细胞输注可显著增加 Tf(hpx/hpx) Hjv(+/+)小鼠而不是 Tf(hpx/hpx) Hjv(-/-)小鼠的铁调素水平。这些结果表明，虽然血红蛋白在转铁蛋白缺乏小鼠中铁调素缺乏的建立或维持中不是必需的，但在铁过载的情况下，血红蛋白对于转铁蛋白依赖性和非依赖性铁调素表达是必需的。
相似文献
1
Hemojuvelin is essential for transferrin-dependent and transferrin-independent hepcidin expression in mice.血红素结合蛋白在小鼠中转铁蛋白依赖性和非依赖性铁调素表达中是必需的。
Haematologica. 2012 Feb;97(2):189-92. doi: 10.3324/haematol.2011.054031. Epub 2011 Oct 11.
2
Transferrin is a major determinant of hepcidin expression in hypotransferrinemic mice.转铁蛋白是低转铁蛋白血症小鼠中铁调素表达的主要决定因素。
Blood. 2011 Jan 13;117(2):630-7. doi: 10.1182/blood-2010-05-287359. Epub 2010 Oct 18.
3
Hepcidin downregulation by repeated bleeding is not mediated by soluble hemojuvelin.反复出血下调铁调素并非通过可溶性转铁蛋白受体介导。
Physiol Res. 2010;59(1):53-59. doi: 10.33549/physiolres.931706. Epub 2009 Feb 27.
4
BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism.骨形态发生蛋白6是铁调素表达和铁代谢的关键内源性调节因子。
Nat Genet. 2009 Apr;41(4):482-7. doi: 10.1038/ng.335. Epub 2009 Mar 1.
5
Neogenin inhibits HJV secretion and regulates BMP-induced hepcidin expression and iron homeostasis.Neogenin 抑制 HJV 的分泌，并调节 BMP 诱导的铁调素表达和铁稳态。
Blood. 2010 Apr 15;115(15):3136-45. doi: 10.1182/blood-2009-11-251199. Epub 2010 Jan 11.
6
Matriptase-2 and Hemojuvelin in Hepcidin Regulation: In Vivo Immunoblot Studies in Mice.Matriptase-2 和 Hemojuvelin 在 Hepcidin 调控中的作用：小鼠体内免疫印迹研究。
Int J Mol Sci. 2021 Mar 6;22(5):2650. doi: 10.3390/ijms22052650.
7
Hepatocyte neogenin is required for hemojuvelin-mediated hepcidin expression and iron homeostasis in mice.肝细胞系新生蛋白在小鼠血红素调节素介导的铁调素表达和铁平衡中是必需的。
Blood. 2021 Aug 12;138(6):486-499. doi: 10.1182/blood.2020009485.
8
An RNAi therapeutic targeting Tmprss6 decreases iron overload in Hfe(-/-) mice and ameliorates anemia and iron overload in murine β-thalassemia intermedia.一种靶向 Tmprss6 的 RNAi 疗法可降低 Hfe(-/-) 小鼠的铁过载，并改善中间型 β-地中海贫血小鼠的贫血和铁过载。
Blood. 2013 Feb 14;121(7):1200-8. doi: 10.1182/blood-2012-09-453977. Epub 2012 Dec 6.
9
Hepcidin-mediated hypoferremic response to acute inflammation requires a threshold of Bmp6/Hjv/Smad signaling.急性炎症时铁调素介导的低铁血症反应需要 Bmp6/Hjv/Smad 信号转导的阈值。
Blood. 2018 Oct 25;132(17):1829-1841. doi: 10.1182/blood-2018-03-841197. Epub 2018 Sep 13.
10
Iron-dependent regulation of hepcidin in Hjv-/- mice: evidence that hemojuvelin is dispensable for sensing body iron levels.铁依赖性调节 Hjv-/- 小鼠中的铁调素：证据表明，血红素结合蛋白对于感应体内铁水平不是必需的。
PLoS One. 2014 Jan 7;9(1):e85530. doi: 10.1371/journal.pone.0085530. eCollection 2014.
引用本文的文献
1
Genetic Susceptibility to Causal Relationship Between Iron Metabolism Disorder Involving Immunocytes and Risk of Pneumonia and Sepsis.涉及免疫细胞的铁代谢紊乱与肺炎和脓毒症风险之间因果关系的遗传易感性。
Food Sci Nutr. 2025 Jun 10;13(6):e70422. doi: 10.1002/fsn3.70422. eCollection 2025 Jun.
2
The ectodomain of matriptase-2 plays an important nonproteolytic role in suppressing hepcidin expression in mice.组织蛋白酶 2 的胞外结构域在抑制小鼠肝脏素表达中发挥重要的非蛋白水解作用。
Blood. 2020 Aug 20;136(8):989-1001. doi: 10.1182/blood.2020005222.
3
The use of hypotransferrinemic mice in studies of iron biology.低转铁蛋白血症小鼠在铁生物学研究中的应用。
Biometals. 2015 Jun;28(3):473-80. doi: 10.1007/s10534-015-9833-0. Epub 2015 Feb 8.
4
The role of hepatic transferrin receptor 2 in the regulation of iron homeostasis in the body.肝脏转铁蛋白受体2在机体铁稳态调节中的作用。
Front Pharmacol. 2014 Mar 6;5:34. doi: 10.3389/fphar.2014.00034. eCollection 2014.
5
Investigating the role of transferrin in the distribution of iron, manganese, copper, and zinc.研究转铁蛋白在铁、锰、铜和锌分布中的作用。
J Biol Inorg Chem. 2014 Aug;19(6):869-77. doi: 10.1007/s00775-014-1118-5. Epub 2014 Feb 25.
6
Bmp6 expression can be regulated independently of liver iron in mice.在小鼠中，Bmp6的表达可以独立于肝脏铁而受到调节。
PLoS One. 2014 Jan 13;9(1):e84906. doi: 10.1371/journal.pone.0084906. eCollection 2014.
7
Iron metabolism: current facts and future directions.铁代谢：当前的事实和未来的方向。
Biochem Med (Zagreb). 2012;22(3):311-28. doi: 10.11613/bm.2012.034.
8
Murine mutants in the study of systemic iron metabolism and its disorders: an update on recent advances.用于系统性铁代谢及其紊乱研究的小鼠突变体：近期进展的最新情况
Biochim Biophys Acta. 2012 Sep;1823(9):1444-50. doi: 10.1016/j.bbamcr.2012.01.011. Epub 2012 Jan 28.
9
Known and potential roles of transferrin in iron biology.转铁蛋白在铁生物学中的已知和潜在作用。
Biometals. 2012 Aug;25(4):677-86. doi: 10.1007/s10534-012-9520-3.
本文引用的文献
1
Transferrin is a major determinant of hepcidin expression in hypotransferrinemic mice.转铁蛋白是低转铁蛋白血症小鼠中铁调素表达的主要决定因素。
Blood. 2011 Jan 13;117(2):630-7. doi: 10.1182/blood-2010-05-287359. Epub 2010 Oct 18.
2
Hepcidin induction by transgenic overexpression of Hfe does not require the Hfe cytoplasmic tail, but does require hemojuvelin.转染过表达 Hfe 基因可诱导铁调素生成，此过程并不需要 Hfe 胞质尾部，但需要依赖膜铁转运蛋白。
Blood. 2010 Dec 16;116(25):5679-87. doi: 10.1182/blood-2010-04-277954. Epub 2010 Sep 13.
3
Iron Loading and Overloading due to Ineffective Erythropoiesis.无效红细胞生成导致的铁负荷与过载
Adv Hematol. 2010;2010:358283. doi: 10.1155/2010/358283. Epub 2010 May 11.
4
The regulation of hepcidin and its effects on systemic and cellular iron metabolism.铁调素的调节及其对全身和细胞铁代谢的影响。
Hematology Am Soc Hematol Educ Program. 2008:151-8. doi: 10.1182/asheducation-2008.1.151.
5
The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin.丝氨酸蛋白酶matriptase-2（TMPRSS6）通过切割膜铁调素（hemojuvelin）来抑制铁调素（hepcidin）的激活。
Cell Metab. 2008 Dec;8(6):502-11. doi: 10.1016/j.cmet.2008.09.012. Epub 2008 Oct 30.
6
A mouse model of juvenile hemochromatosis.青少年血色素沉着症的小鼠模型
J Clin Invest. 2005 Aug;115(8):2187-91. doi: 10.1172/JCI25049.
7
Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload.血色素沉着症相关蛋白对于膳食铁感知至关重要，其突变会导致严重的铁过载。
J Clin Invest. 2005 Aug;115(8):2180-6. doi: 10.1172/JCI25683.
8
Regulators of iron balance in humans.人体铁平衡的调节因子。
Blood. 1994 Sep 15;84(6):1697-702.
Zotero 插件