Placental leptin receptor isoforms in normal and pathological pregnancies
Placental leptin receptor isoforms in normal and pathological pregnancies
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DOI：
10.1053/plac.2002.0805
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发表时间：
2003-01-01
期刊：
影响因子：
3.8
通讯作者：
Hauguel-de Mouzon, S
中科院分区：
文献类型：
--
作者：
Challier, J;Galtier, M;Hauguel-de Mouzon, S
人瘦素受体的mRNA剪接产生四种具有不同C-末端序列的膜亚型。它们的不同之处在于其细胞内结构域的长度，其中包括对瘦素信号传导的特异性至关重要的特定基序。作为功能研究的一步，我们已经确定了正常妊娠和糖尿病和先兆子痫相关妊娠的人胎盘中瘦素受体的特征。瘦素和瘦素受体可视化的免疫组化胎盘从第一和第三孕期。针对N和C-末端表位的抗体显示在早期和长期胎盘绒毛以及JAr和BeWo衍生的滋养层细胞中的合体滋养层的顶膜中的信号。此外，一个独特的亚型识别其细胞外质膜表位是专门定位在细胞滋养层细胞和可能的染色的可溶性受体。与跨膜受体相反，这种异构体的表达增加，在胎盘的先兆子痫和糖尿病妇女合成更多的瘦素比胎盘从uncomplicated pregnancy.These数据表明，短和长的跨膜瘦素受体表达在滋养层细胞，并表明，瘦素在胎盘内合成可以通过这两种受体异构体发挥局部作用。由于也可从母体来源获得瘦素，这些跨膜受体在妊娠中可能具有正常和增加的瘦素产生的不同信号。共同定位。瘦素和可溶性受体同种型的结合表明，这种同种型通过改变瘦素结合能力来调节母体游离瘦素水平。(C)2002爱思唯尔科技有限公司版权所有。
Alternate mRNA splicing of human leptin receptor generates four membrane isoforms with different C-terminal sequences. They differ by the length of their intracellular domain which include specific motifs crucial for the specificity of leptin signalling. As a step towards functional studies, we have characterized leptin receptors in human placenta from normal pregnancies and pregnancies associated with diabetes and pre-eclampsia. Leptin and leptin receptors were visualized by immunohistochemistry of placentas obtained from first and third trimester pregnancies. Antibodies against N and C-terminal epitopes showed signals in the apical membrane of the syncytiotrophoblast in early and term placental villi as well As in JAr and BeWo derived trophoblast cells. In addition, a distinct isoform recognized by its extracellular juxtamembrane epitope was exclusively localized in cytotrophoblast cells and likely stains the soluble receptor. At contrast with the transmembrane receptors, the expression of this isoform is increased in placentas of pre-eclamptic and diabetic women which synthesize more leptin than placenta from uncomplicated pregnancy.These data demonstrate that short and long transmembrane leptin receptors are expressed in the trophoblast and indicate that leptin synthetized within the placenta can act locally through both receptor isoforms. Being also accessible to leptin from maternal origin, these transmembrane receptors may signal differently in pregnancy with normal and increased leptin production. The co-localization. of leptin and the soluble receptor isoform suggests that this isoform serves for modulating maternal free leptin levels through modification of leptin binding capacities. (C) 2002 Elsevier Science Ltd. All rights reserved.