Madan Ashima, Varma Sushama, Cohen Harvey J
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305-5208, USA.
Mol Genet Metab. 2002 Mar;75(3):244-9. doi: 10.1006/mgme.2001.3293.
Erythropoietin (Epo) is a glycoprotein hormone that is the primary regulator of erythropoiesis. Transcription of the Epo gene increases in response to hypoxia or anemia. Epo is synthesized in the liver in fetal life and in the kidney later in gestation. In the mammalian fetus the switch in Epo production from the liver to the kidney occurs in the third trimester. Hypoxia-inducible factor (HIF-1) is a heterodimeric transcription factor consisting of an alpha and beta subunit that binds under hypoxic conditions to an enhancer element in the 3' region of the Epo gene. In order to determine if there is a relationship between expression of HIF-1 alpha and beta subunits with the shift in expression of the Epo gene from the liver to the kidney or with the transitional events occurring at birth we analyzed the expression of these mRNAs in mouse and human fetuses at different stages of gestation. Total RNA was extracted from the brain, heart, kidney, liver, and lungs of mice at P15, P17, and P19 of gestation, from newborn mice at Days 1 and 3, from an adult and an anemic adult mouse as well as from human fetuses at 14-22 weeks of gestation. RNA was analyzed by Northern blot and slot-blot hybridization using appropriate cDNA probes. HIF-1alpha and -beta mRNA were expressed in all tissues tested and at all stages of gestation in the mouse and human fetus. Expression of HIF-1alpha and -beta in the mouse fetus was highest in the brain followed by heart, kidney, lung, and liver. Expression in the fetal and newborn mice was higher versus the adult and expression was higher in the anemic versus the normal adult mouse. In the human fetus a higher expression of HIF-1alpha was noted in the brain followed by heart, kidney, lung, and liver. There was a small trend toward a decrease in expression with advancing gestational age. HIF-1beta was expressed to a similar extent in all human tissues examined. Our studies indicate that expression of HIF-1alpha and -beta subunits was not related to the switch in Epo gene expression from the liver to the kidney. Although expression of HIF-1alpha and -beta did not decrease immediately after birth, it is possible that the HIF-1 protein is involved in the various events that occur during transition after birth.
促红细胞生成素（Epo）是一种糖蛋白激素，是红细胞生成的主要调节因子。Epo基因的转录会因缺氧或贫血而增加。在胎儿期，Epo在肝脏中合成，在妊娠后期则在肾脏中合成。在哺乳动物胎儿中，Epo产生部位从肝脏向肾脏的转变发生在妊娠晚期。缺氧诱导因子（HIF-1）是一种异二聚体转录因子，由一个α亚基和一个β亚基组成，在缺氧条件下与Epo基因3'区域的增强子元件结合。为了确定HIF-1α和β亚基的表达与Epo基因表达从肝脏向肾脏的转变之间是否存在关系，或者与出生时发生的过渡事件之间是否存在关系，我们分析了这些mRNA在不同妊娠阶段的小鼠和人类胎儿中的表达情况。从妊娠第15、17和19天的小鼠的脑、心脏、肾脏、肝脏和肺中提取总RNA，从出生第1天和第3天的新生小鼠、成年小鼠和贫血成年小鼠以及妊娠14 - 22周的人类胎儿中提取总RNA。使用适当的cDNA探针通过Northern印迹和狭缝印迹杂交分析RNA。HIF-1α和-β mRNA在小鼠和人类胎儿的所有测试组织以及妊娠的所有阶段均有表达。小鼠胎儿中HIF-1α和-β的表达在脑中最高，其次是心脏、肾脏、肺和肝脏。胎儿和新生小鼠中的表达高于成年小鼠，贫血成年小鼠中的表达高于正常成年小鼠。在人类胎儿中，HIF-1α在脑中的表达较高，其次是心脏、肾脏、肺和肝脏。随着胎龄增加，表达有轻微下降趋势。HIF-1β在所有检测的人类组织中的表达程度相似。我们的研究表明，HIF-1α和-β亚基的表达与Epo基因表达从肝脏向肾脏的转变无关。虽然出生后HIF-1α和-β的表达没有立即下降，但HIF-1蛋白有可能参与出生后过渡期间发生的各种事件。
