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Blood:Erythroferrone(ERFE)可抑制BMP5/6/7诱导的铁调素合成

2018-08-15 MedSci MedSci原创

中心点:Erythroferrone(ERFE)在体内外均可抑制BMP/SMAD信号。ERFE通过BMP5、BMP6和BMP7抑制铁调素诱导。摘要:铁调素降低可动员铁,促进红细胞生成,但铁过量是β-地中海贫血的致病机制。促红细胞生成素(EPO)可通过增加有核红细胞来增强ERFE合成,而ERFE可抑制肝脏铁调素合成,其潜在机制尚不明确。肝脏的BMP/SMAD信号通路对于铁调素的调控至关重要,Joao

中心点:

Erythroferrone(ERFE)在体内外均可抑制BMP/SMAD信号。

ERFE通过BMP5、BMP6和BMP7抑制铁调素诱导。

摘要:

铁调素降低可动员铁,促进红细胞生成,但铁过量是β-地中海贫血的致病机制。促红细胞生成素(EPO)可通过增加有核红细胞来增强ERFE合成,而ERFE可抑制肝脏铁调素合成,其潜在机制尚不明确。

肝脏的BMP/SMAD信号通路对于铁调素的调控至关重要,Joao Arezes等研究人员发现,在体内,EPO可部分通过ERFE依赖性方式抑制铁调素和其他BMP靶基因。而且,重组ERFE对肝BMP/SMAD通路的抑制独立于血清和肝铁的变化,ERFE可降低SMAD1/5/8的磷酸化、抑制BMP靶基因的表达。

ERFE可特异性消除BMP5、BMP6和BMP7对铁调素的诱导,但对BMP2、BMP4、BMP9或激活素B所诱导的铁调素没有或几乎没有影响。无细胞HTRF实验表明BMP5、BMP6和BMP7可与抗-ERFE竞争结合ERFE。

综上所述,ERFE通过优先抑制BMP5、BMP6和BMP7来抑制肝BMP/SMAD信号,从而降低铁调素。ERFE可作为激活的有核红细胞合成的自然配体陷阱来调节铁的可用性。

原始出处:

Joao Arezes, et al. Erythroferrone inhibits the induction of hepcidin by BMP6. Blood  2018  :blood-2018-06-857995;  doi: https://doi.org/10.1182/blood-2018-06-857995

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    2018-11-12 heli0118
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    2019-03-23 surilei
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    2018-08-30 zhs3882
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