Preeclampsia is associated with alterations in insulin-like growth factor (IGF)-1 and IGF-Binding proteins in Wharton's jelly of the umbilical cord

Preeclampsia is associated with alterations in insulin-like growth factor (IGF)-1 and IGF-Binding proteins in Wharton's jelly of the umbilical cord
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DOI:
10.1515/cclm.2000.087
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发表时间:
2000-07-01
影响因子:
6.8
通讯作者:
Jaworski, S
Jaworski, S
中科院分区:
医学2区
文献类型:
--
作者:
Bankowski, E;Palka, J;Jaworski, S

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华顿氏胶富含细胞外基质,细胞外基质被认为是细胞附近聚集和稳定生长因子的储存场所。以前发现,华顿氏果冻含有大量的胰岛素样生长因子(IGF)-1和IGF结合蛋白(BP)。IGF-1是胶原蛋白和硫酸化糖胺聚糖生物合成的刺激剂。先兆子痫(水肿、蛋白尿、高血压(EPH)妊娠中毒)伴随着硫酸化糖胺聚糖在华顿氏胶中的积累。IGF-1和BP可能在这种组织的重塑中发挥重要作用。决定评估先兆子痫母亲分娩的新生儿华顿氏胶中IGF-1和BP的量的变化。对10名对照和10名患有先兆子痫的母亲所产的新生儿(水肿,蛋白尿> 500 mg/l,动脉压:收缩压> 140 mm Hg,舒张压>90 mm Hg)的沃顿氏胶进行研究。采用放射免疫技术测定IGF-1和IGF-BP(BP-1和BP-3)。研究发现,先兆子痫与华顿氏胶中IGF-1和IGF-BP-1的减少有关。配体印迹法证实BP-3(而非BP-1)是华顿氏胶中结合IGF-1的主要成分。肝素显著抑制IGF-1与BP-3的结合。从我们以前的研究中得知,先兆子痫与华顿氏胶中硫酸化糖胺聚糖(肝素、硫酸乙酰肝素、硫酸皮肤素)的量增加有关。这可能是一个因素,它阻止了IGF-1的结合BP和促进IGF-1与细胞的结合,刺激它们产生硫酸化的糖胺聚糖在华顿氏胶。
Wharton's jelly is abundant in extracellular matrix, which is known as a storage site to concentrate and stabilise growth factors in the vicinity of cells. It was previously found that Wharton's jelly contains significant amounts of insulin-like growth factor (IGF)-1 and IGF-binding proteins (BPs). IGF-1 is a stimulator of biosynthetics of collagen and sulphated glycosaminoglycans. Preeclampsia (edema, proteinuria, hypertension (EPH)gestosis) is accompanied by an accumulation of sulphated glycosaminoglycans in Wharton's jelly. IGF-1 and BPs may play an important role in such a remodelling of this tissue. It was decided to evaluate the alterations in amounts of IGF-1 and BPs in Wharton's jelly of newborns delivered by mothers with preeclampsia. Studies were performed on Wharton's jelly of 10 controls and 10 newborns delivered by mothers with preeclampsia (edema, proteinuria > 500 mg/l, arterial pressure: systolic > 140 mm Hg, diastolic >90 mmHg). Radioimmunological techniques were employed to determine IGF-1 and IGF-BPs (BP-1 and BP-3). It was found that preeclampsia is associated with a decrease in IGF-1-and IGF-BP-1 in Wharton's jelly. A slight increase in IGF-BP-3 was found. Liga nd blotting demonstrated that BP-3 (not BP-1) is a main component of Wharton's jelly which binds IGF-1. Heparin drastically inhibited the binding of IGF-1 by BP-3. It is known from our previous studies that preeclampsia is associated with an increase in the amount of sulphated glycosaminoglycans (heparin, heparan sulphate, dermatan sulphate) in Wharton's jelly. This may be a factor, which prevents the binding of IGF-1 by BPs and facilitates the binding of IGF-1 to cells, stimulating them to produce sulphated glycosaminoglycans in Wharton's jelly.