Smad7 deficiency decreases iron and haemoglobin through hepcidin up-regulation by multilayer compensatory mechanisms
文献类型：期刊论文
| 作者 | An, Peng2,3; Wang, Hao2,3; Wu, Qian2,3; Wang, Jiaming2,3; Xia, Zhidan2,3; He, Xuyan2,3; Wang, Xinhui2,3; Min, Junxia2,3; Wang, Fudi1,2,3; Wang, Hao1 |
| 刊名 | JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
 |
| 出版日期 | 2018 |
| 卷号 | 22期号:6页码:3035-3044 |
| 关键词 | Bambi follistatin hepcidin iron deficiency Smad6 Smad7 |
| ISSN号 | 1582-4934 |
| DOI | 10.1111/jcmm.13546 |
| 文献子类 | Article |
| 英文摘要 | 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-beta signalling as one of the most relevant pathways, including the up-regulated genes Smad6, Bambi and Fst (Follistatin). We found that Smad6 and Bambibut not Follistatinare 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. |
| 学科主题 | Cell Biology ; Research & Experimental Medicine |
| WOS关键词 | BONE-MORPHOGENETIC PROTEIN ; HEREDITARY HEMOCHROMATOSIS ; INFLAMMATORY RESPONSES ; MOUSE MODEL ; RNA-SEQ ; EXPRESSION ; MICE ; OVERLOAD ; LIVER ; HOMEOSTASIS |
| 语种 | 英语 |
| WOS记录号 | WOS:000433580300008 |
| 出版者 | WILEY |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/732]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Zhengzhou Univ, Sch Publ Hlth, Precis Nutr Innovat Ctr, Zhengzhou, Henan, Peoples R China; 2.China Agr Univ, Beijing Adv Innovat Ctr Food Nutr & Human Hlth, Beijing, Peoples R China; 3.Zhejiang Univ, Affiliated Hosp 1, Collaborat Innovat Ctr Diag & Treatment Infect Di, Sch Publ Hlth,Inst Translat Med,Sch Med, Hangzhou, Zhejiang, Peoples R China; 4.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai, Peoples R China, |
| 推荐引用方式 GB/T 7714 | An, Peng,Wang, Hao,Wu, Qian,et al. Smad7 deficiency decreases iron and haemoglobin through hepcidin up-regulation by multilayer compensatory mechanisms[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2018,22(6):3035-3044. |
| APA | An, Peng.,Wang, Hao.,Wu, Qian.,Wang, Jiaming.,Xia, Zhidan.,...&,.(2018).Smad7 deficiency decreases iron and haemoglobin through hepcidin up-regulation by multilayer compensatory mechanisms.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,22(6),3035-3044. |
| MLA | An, Peng,et al."Smad7 deficiency decreases iron and haemoglobin through hepcidin up-regulation by multilayer compensatory mechanisms".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 22.6(2018):3035-3044. |
入库方式： OAI收割
来源：上海营养与健康研究所
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