Smad7 deficiency decreases iron and haemoglobin through hepcidin up-regulation by multilayer compensatory mechanisms.
Smad7 deficiency decreases iron and haemoglobin through hepcidin up-regulation by multilayer compensatory mechanisms.
复制标题
Smad7 缺乏通过多层补偿机制上调铁调素来降低铁和血红蛋白
DOI：
10.1111/jcmm.13546
复制
发表时间：
2018-06
影响因子：
5.3
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
An P;Wang H;Wu Q;Wang J;Xia Z;He X;Wang X;Chen Y;Min J;Wang F
To maintain iron homoeostasis, the iron regulatory hormone hepcidin is tightly controlled by BMP‐Smad signalling pathway, but the physical role of Smad7 in hepcidin regulation remains elastic. We generated and characterized heptatocyte‐specific Smad7 knockout mice (Smad7 Alb/Alb), which showed decreased serum iron, tissue iron, haemoglobin concentration, up‐regulated hepcidin and increased phosphor‐Smad1/5/8 levels in both孤立的原发性肝细胞和肝组织。离子。肝脏中的不同表达的基因被映射到途径上，揭示了TGF -β信号作为最相关的途径之一，包括上调的基因SMAD6 SMAD6，BAMBI和FST（FOL）细胞中的Ollistatin显着降低了肝素表达。 SMAD7通过负控制肝素表达来充当铁同骨的关键调节剂，而SMAD6和SMAD7具有非冗余的作用。
To maintain iron homoeostasis, the iron regulatory hormone hepcidin is tightly controlled by BMP‐Smad signalling pathway, but the physiological role of Smad7 in hepcidin regulation remains elusive. We generated and characterized hepatocyte‐specific Smad7 knockout mice (Smad7 Alb/Alb), which showed decreased serum iron, tissue iron, haemoglobin concentration, up‐regulated hepcidin and increased phosphor‐Smad1/5/8 levels in both isolated primary hepatocytes and liver tissues. Increased levels of hepcidin lead to reduced expression of intestinal ferroportin and mild iron deficiency anaemia. Interestingly, we found no difference in hepcidin expression or phosphor‐Smad1/5/8 levels between iron‐challenged Smad7 Alb/Alb and Smad7 flox/flox, suggesting other factors assume the role of iron‐induced hepcidin regulation in Smad7 deletion. We performed RNA‐seq to identify differentially expressed genes in the liver. Significantly up‐regulated genes were then mapped to pathways, revealing TGF‐β signalling as one of the most relevant pathways, including the up‐regulated genes Smad6, Bambi and Fst (Follistatin). We found that Smad6 and Bambi—but not Follistatin—are controlled by the iron‐BMP–Smad pathway. Overexpressing Smad6, Bambi or Follistatin in cells significantly reduced hepcidin expression. Smad7 functions as a key regulator of iron homoeostasis by negatively controlling hepcidin expression, and Smad6 and Smad7 have non‐redundant roles. Smad6, Bambi and Follistatin serve as additional inhibitors of hepcidin in the liver.
登录
查看更多内容
影响因子：
168.9
作者：
Bridle, KR;Frazer, DM;Ramm, GA
通讯作者：
Ramm, GA
影响因子：
11.4
作者：
Karaulanov, E;Knöchel, W;Niehrs, C
通讯作者：
Niehrs, C
影响因子：
20.3
作者：
Finberg, Karin E.;Whittlesey, Rebecca L.;Andrews, Nancy C.
通讯作者：
Andrews, Nancy C.
影响因子：
4.4
作者：
Li, Ronggui;Rosendahl, Alexander;Heuchel, Rainer L.
通讯作者：
Heuchel, Rainer L.
DOI：
10.1073/pnas.95.16.9337
发表时间：
1998-08-04
影响因子：
11.1
作者：
Iemura, S;Yamamoto, TS;Ueno, N
通讯作者：
Ueno, N