Erythropoietin contributes to implantation: Ectopic hemoglobin synthesis in decidual cells of mice
Erythropoietin contributes to implantation: Ectopic hemoglobin synthesis in decidual cells of mice
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DOI：
10.1111/j.1741-4520.2006.00137.x
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发表时间：
2007-03
影响因子：
1.3
通讯作者：
Y. Yasuda;Tohru Sasaki;M. Takagawa;M. Maeda;Megumi Yasuda;T. Atsumi;Y. Fujita;H. Fujita
中科院分区：
文献类型：
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作者：
Y. Yasuda;Tohru Sasaki;M. Takagawa;M. Maeda;Megumi Yasuda;T. Atsumi;Y. Fujita;H. Fujita
摘要促红细胞生成素通过与其受体结合，通过上调红细胞特异性基因刺激永久性成红细胞积累血红蛋白（Hb），并导致成红细胞分化为红细胞。在小鼠蜕膜中，我们发现了促红细胞生成素受体的转录本的表达，其功能尚未阐明。促红细胞生成素信号被抑制注射的促红细胞生成素受体的可溶性形式，能够结合促红细胞生成素到小鼠子宫腔的妊娠第4天，和苍白和有缺陷的蜕膜体出现三天后。这些苍白的蜕膜体含有缺陷胚胎，没有延伸到胎盘外区域，而正常的红色蜕膜体含有正常发育的胚胎，并表达胚胎和成人Hb，其各自血红蛋白的特征性位置证实了β-或β-珠蛋白信号。此外，阻断促红细胞生成素信号转导破坏了含Hb的细胞，导致细胞凋亡，从而导致胚胎死亡。因此，促红细胞生成素介导的Hb合成对于蜕膜细胞的存活至关重要。此外，虽然没有检测到加塔-1和红细胞血红素酶的转录物，但β珠蛋白基因以及非特异性δ-氨基乙酰丙酸合酶以促红细胞生成素依赖性方式表达和调节。这是第一个证据表明，异位血红蛋白合成存在，促红细胞生成素共调节红细胞（珠蛋白）和非红细胞（δ-氨基乙酰丙酸合成酶）基因。
ABSTRACT Erythropoietin, by binding to its receptor, stimulates definitive erythroblasts to accumulate hemoglobin (Hb) by up‐regulating erythroid‐specific genes and causes differentiation of erythroblasts into erythrocytes. In mouse decidua we have found the expression of transcripts for the erythropoietin receptor, the function of which has not yet been elucidated. Erythropoietin signaling was inhibited by the injection of a soluble form of the erythropoietin receptor capable of binding with erythropoietin into the mouse uterine cavity on day 4 of gestation, and pale and defective decidual bodies appeared three days later. These pale decidual bodies contained defective embryos without extension to the ectoplacental region, while normal reddish decidual bodies contained normal developing embryos and expressed embryonic and adult Hb with characteristic location of the respective hemoglobins in which an ɛ‐ or β‐globin signal was confirmed. Furthermore, blocking of erythropoietin signaling destroyed Hb‐containing cells and resulted in apoptosis that caused embryonic death. Thus, erythropoietin‐mediated Hb synthesis is essential for the survival of decidual cells. In addition, although no transcripts for GATA‐1 and erythroid heme enzymes could be detected, genes for β‐globin, as well as non‐specific δ‐aminolevulinate synthase, were expressed and regulated in an erythropoietin‐dependent manner. This is the first evidence that ectopic Hb synthesis exists and that erythropoietin coregulates erythroid (globin) and nonerythroid (δ‐aminolevulinate synthase) genes.