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

本文系梅斯医学(MedSci)原创编译,转载需授权!

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (4)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1634041, encodeId=68dc163404144, content=<a href='/topic/show?id=596635e549' target=_blank style='color:#2F92EE;'>#BMP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3575, encryptionId=596635e549, topicName=BMP)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Mon Nov 12 05:13:00 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1703588, encodeId=b8131e03588f4, content=<a href='/topic/show?id=0d2869594b' target=_blank style='color:#2F92EE;'>#ERR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6959, encryptionId=0d2869594b, topicName=ERR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a72d30527892, createdName=surilei, createdTime=Sat Mar 23 12:13:00 CST 2019, time=2019-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1943609, encodeId=00cd1943609a2, content=<a href='/topic/show?id=2165694233' target=_blank style='color:#2F92EE;'>#ERFE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6942, encryptionId=2165694233, topicName=ERFE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b952312, createdName=zhs3882, createdTime=Thu Aug 30 17:13:00 CST 2018, time=2018-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1360392, encodeId=3aad1360392e4, content=<a href='/topic/show?id=fe70965643d' target=_blank style='color:#2F92EE;'>#铁调素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96564, encryptionId=fe70965643d, topicName=铁调素)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9c94141, createdName=liuquanmn, createdTime=Fri Aug 17 02:13:00 CST 2018, time=2018-08-17, status=1, ipAttribution=)]
    2018-11-12 heli0118
  2. [GetPortalCommentsPageByObjectIdResponse(id=1634041, encodeId=68dc163404144, content=<a href='/topic/show?id=596635e549' target=_blank style='color:#2F92EE;'>#BMP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3575, encryptionId=596635e549, topicName=BMP)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Mon Nov 12 05:13:00 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1703588, encodeId=b8131e03588f4, content=<a href='/topic/show?id=0d2869594b' target=_blank style='color:#2F92EE;'>#ERR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6959, encryptionId=0d2869594b, topicName=ERR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a72d30527892, createdName=surilei, createdTime=Sat Mar 23 12:13:00 CST 2019, time=2019-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1943609, encodeId=00cd1943609a2, content=<a href='/topic/show?id=2165694233' target=_blank style='color:#2F92EE;'>#ERFE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6942, encryptionId=2165694233, topicName=ERFE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b952312, createdName=zhs3882, createdTime=Thu Aug 30 17:13:00 CST 2018, time=2018-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1360392, encodeId=3aad1360392e4, content=<a href='/topic/show?id=fe70965643d' target=_blank style='color:#2F92EE;'>#铁调素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96564, encryptionId=fe70965643d, topicName=铁调素)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9c94141, createdName=liuquanmn, createdTime=Fri Aug 17 02:13:00 CST 2018, time=2018-08-17, status=1, ipAttribution=)]
    2019-03-23 surilei
  3. [GetPortalCommentsPageByObjectIdResponse(id=1634041, encodeId=68dc163404144, content=<a href='/topic/show?id=596635e549' target=_blank style='color:#2F92EE;'>#BMP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3575, encryptionId=596635e549, topicName=BMP)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Mon Nov 12 05:13:00 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1703588, encodeId=b8131e03588f4, content=<a href='/topic/show?id=0d2869594b' target=_blank style='color:#2F92EE;'>#ERR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6959, encryptionId=0d2869594b, topicName=ERR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a72d30527892, createdName=surilei, createdTime=Sat Mar 23 12:13:00 CST 2019, time=2019-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1943609, encodeId=00cd1943609a2, content=<a href='/topic/show?id=2165694233' target=_blank style='color:#2F92EE;'>#ERFE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6942, encryptionId=2165694233, topicName=ERFE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b952312, createdName=zhs3882, createdTime=Thu Aug 30 17:13:00 CST 2018, time=2018-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1360392, encodeId=3aad1360392e4, content=<a href='/topic/show?id=fe70965643d' target=_blank style='color:#2F92EE;'>#铁调素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96564, encryptionId=fe70965643d, topicName=铁调素)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9c94141, createdName=liuquanmn, createdTime=Fri Aug 17 02:13:00 CST 2018, time=2018-08-17, status=1, ipAttribution=)]
    2018-08-30 zhs3882
  4. [GetPortalCommentsPageByObjectIdResponse(id=1634041, encodeId=68dc163404144, content=<a href='/topic/show?id=596635e549' target=_blank style='color:#2F92EE;'>#BMP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3575, encryptionId=596635e549, topicName=BMP)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Mon Nov 12 05:13:00 CST 2018, time=2018-11-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1703588, encodeId=b8131e03588f4, content=<a href='/topic/show?id=0d2869594b' target=_blank style='color:#2F92EE;'>#ERR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6959, encryptionId=0d2869594b, topicName=ERR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a72d30527892, createdName=surilei, createdTime=Sat Mar 23 12:13:00 CST 2019, time=2019-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1943609, encodeId=00cd1943609a2, content=<a href='/topic/show?id=2165694233' target=_blank style='color:#2F92EE;'>#ERFE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6942, encryptionId=2165694233, topicName=ERFE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b952312, createdName=zhs3882, createdTime=Thu Aug 30 17:13:00 CST 2018, time=2018-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1360392, encodeId=3aad1360392e4, content=<a href='/topic/show?id=fe70965643d' target=_blank style='color:#2F92EE;'>#铁调素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96564, encryptionId=fe70965643d, topicName=铁调素)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=9c94141, createdName=liuquanmn, createdTime=Fri Aug 17 02:13:00 CST 2018, time=2018-08-17, status=1, ipAttribution=)]

相关资讯

Lancet Haematology:缺铁妇女补铁方案比较研究

对于缺铁女性,将每日补充的铁剂分开服用会导致血清铁调素浓度升高影响铁吸收。研究认为,将每日的补充铁剂一次性服用,隔日1次是最优的补铁方案

Crit Care Med:外科重症监护患者铁调素和贫血!

由此可见,入住ICU时铁调素血清浓度明显增加,并在ICU停留期间(28天)显著降低。降低的铁调素浓度与增加的网织红细胞反应和通过减少IL-6和C反应蛋白浓度来体现减弱的炎症反应有关,但与贫血痊愈无关。

Blood:研究人员揭示了铁调素在感染中的功能’

Stefanova等人提供了直接证据证明了铁调素是先天免疫的主要成分

Blood:敲除BMP6可恶化HJV缺陷小鼠的表型,并降低铁调素在LPS刺激后所能达到的水平。

小鼠缺乏BMP6或其共受体铁调素调节蛋白(HJV)均可导致雄鼠铁调素不足、肝脏铁负荷以及肝外铁累积的相似表型。这一点与HJV在肝脏是BMP6的共受体的观点相一致。

Blood:ERFE,一种新发现的激素,在红细胞生成过程中的作用。

ERFE是有核红细胞受促红细胞生成素刺激后分泌的一种糖蛋白类激素,可抑制铁调素的表达,从而增加铁的吸收和动员。

Blood:抑免蛋白FKBP12通过结合BMP1型受体ALK2抑制铁调素的表达。

在铁、炎症和药物的刺激下,经过BMP-SMAD通路,以及抑制mTOR与抑免蛋白FKBP12复合的雷帕霉素,激活了调节铁平衡的肝调素的关键调控的表达。FKBP12与BMP1型受体相互作用,避免不受控制的信号。通过药理学和基因研究,研究人员发现FKBP12具有调节铁调素的功能。在体外和小鼠肝脏细胞中,通过雷帕霉素或者他克莫司封闭FKBP12均可激活铁调素。