Blood：急性炎症时，铁调素介导的低铁反应需要一定阈值的Bmp6/Hjv/Smad信号

2018-09-15 MedSci MedSci原创

中心点：Hjv-/-小鼠不能对急性炎症产生合适的低铁反应。Hjv通过维持Bmp6/Smad信号刺激肝细胞铁调素的阈值来促进炎性低铁反应。摘要：系统铁平衡受铁调素控制，这是一种肝脏激素，通过促进靶细胞的铁输出蛋白降解来限制铁流到血液中。铁依赖性铁调素诱导需要铁调素调节蛋白（HJV）的存在；HJV是一种骨形成蛋白（BMP）的共受体，在幼年型血色病中被破坏，导致明显的铁调素缺乏和组织铁过负荷。Hjv-/

中心点：

Hjv-/-小鼠不能对急性炎症产生合适的低铁反应。

Hjv通过维持Bmp6/Smad信号刺激肝细胞铁调素的阈值来促进炎性低铁反应。

摘要：

系统铁平衡受铁调素控制，这是一种肝脏激素，通过促进靶细胞的铁输出蛋白降解来限制铁流到血液中。铁依赖性铁调素诱导需要铁调素调节蛋白（HJV）的存在；HJV是一种骨形成蛋白（BMP）的共受体，在幼年型血色病中被破坏，导致明显的铁调素缺乏和组织铁过负荷。Hjv-/-小鼠可再现血色素沉着病的表型特征，但在脂多糖（LPS）处理后会出现钝性铁调素诱导。

研究人员发现Hjv-/-小鼠不能对LPS、脂肽FSL1或大肠杆菌感染诱导的急性炎症产生适合的低铁反应，因为残余的铁调素不足以彻底降低巨噬细胞的铁蛋白水平。Hfe-/-小鼠，一种轻度血色素沉着病的模型，表现出近似野生型小鼠的炎性铁调素表达和相关作用，而Hjv-/-Hfe-/-小鼠则表现为单Hjv-/-小鼠的表型。

在原代小鼠肝细胞中，Hjv缺陷不影响IL-6/Stat，只轻微抑制肝调素的BMP2/Smad信号；但其严重破坏BMP6/Sma信号，进而影响与IL-6/Stat信号的协同作用。在缺铁的野生型小鼠中，铁调素的炎性诱导被抑制，予以富含铁食物后可恢复。

总而言之，铁调素诱导炎症需要Hjv的参与，Hjv通过维持Bmp6/Smad信号的阈值来调控急性低铁反应。Hjv或可作为炎性贫血的潜在药物靶点。

原始出处：

Carine Fillebeen， et al.Hepcidin-mediated hypoferremic response to acute inflammation requires a threshold of Bmp6/Hjv/Smad signaling.Blood 2018 ：blood-2018-03-841197； doi： https：//doi.org/10.1182/blood-2018-03-841197

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2019-02-24 hywen7326

#HJV#

42 0
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2019-06-04 HNYYM

#BMP#

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2019-08-15 wshxjq

#Smad#

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2018-09-17 liuquanmn

#铁调素#

0 0
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2018-09-17 江川靖瑶

#SMA#

44 0
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2018-09-17 canlab

#BMP6#

37 0
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2018-09-17 qjddjq

#阈值#

33 0

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Blood：急性炎症时，铁调素介导的低铁反应需要一定阈值的Bmp6/Hjv/Smad信号

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