旁分泌信号
红细胞生成
调解人
无效红细胞生成
海西定
生物
内科学
内分泌学
铁转运蛋白
造血
缺铁
生产过剩
医学
铁蛋白
促红细胞生成素
贫血
受体
作者
Richard Coffey,Chun-Ling Grace Jung,Joseph Daniel Olivera,Gabriel Karin,Renata C. Pereira,Elizabeta Nemeth,Tomas Ganz
出处
期刊:Blood
[American Society of Hematology]
日期:2022-01-20
卷期号:139 (3): 439-451
被引量:7
标识
DOI:10.1182/blood.2021014054
摘要
The hormone erythroferrone (ERFE) is produced by erythroid cells in response to hemorrhage, hypoxia, or other erythropoietic stimuli, and it suppresses the hepatic production of the iron-regulatory hormone hepcidin, thereby mobilizing iron for erythropoiesis. Suppression of hepcidin by ERFE is believed to be mediated by interference with paracrine bone morphogenetic protein (BMP) signaling that regulates hepcidin transcription in hepatocytes. In anemias with ineffective erythropoiesis, ERFE is pathologically overproduced, but its contribution to the clinical manifestations of these anemias is not well understood. We generated 3 lines of transgenic mice with graded erythroid overexpression of ERFE and found that they developed dose-dependent iron overload, impaired hepatic BMP signaling, and relative hepcidin deficiency. These findings add to the evidence that ERFE is a mediator of iron overload in conditions in which ERFE is overproduced, including anemias with ineffective erythropoiesis. At the highest levels of ERFE overexpression, the mice manifested decreased perinatal survival, impaired growth, small hypofunctional kidneys, decreased gonadal fat depots, and neurobehavioral abnormalities, all consistent with impaired organ-specific BMP signaling during development. Neutralizing excessive ERFE in congenital anemias with ineffective erythropoiesis may not only prevent iron overload but may have additional benefits for growth and development.
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