Adrenomedullin is decreased in preeclampsia because of failed response to epidermal growth factor and impaired syncytialization
Adrenomedullin is decreased in preeclampsia because of failed response to epidermal growth factor and impaired syncytialization
复制标题
DOI：
10.1161/01.hyp.0000095613.41961.6e
复制
发表时间：
2003-11-01
期刊：
影响因子：
8.3
通讯作者：
Morrish, DW
中科院分区：
文献类型：
--
作者：
Li, HS;Dakour, J;Morrish, DW
为了探讨正常和子痫前期(PE)状态下肾上腺髓质素(ADM)的调节机制，我们测定了胎盘ADM的产生以及细胞因子对ADM的调节。从正常胎盘(n=8)和胎盘胎盘(n=10)分离纯化的细胞滋养层细胞，在不加或不加10 ng/m L表皮生长因子(EGF)、1 ng/m L转化生长因子(TGF)-β1、10 ng/m L肿瘤坏死因子(TNF)-α或100 U/m L干扰素-γ的条件下培养3d。细胞在10%胎牛血清中培养3d，桥粒蛋白染色检测合体形成情况。对正常胎盘和PE胎盘进行快速冰冻，检测ADM基因的表达。结果表明，用放射免疫法测定PE胎盘细胞培养上清液中ADM的基础产量显著低于对照组。EGF可显著刺激正常滋养层细胞产生ADM，但对PE胎盘无明显作用。无论是正常胎盘还是PE胎盘，肿瘤坏死因子-α、转化生长因子-β1或干扰素-γ都不能改变ADM的分泌。Northern印迹分析显示PE胎盘组织中ADM基因表达下降34.3+/-8.3%。在PE胎盘中，合胞化减少(第3天：正常，16.7+/-1.3%；PE，5.5+/-2.0%；P
To explore the mechanisms of adrenomedullin (ADM) regulation in normal and preeclamptic (PE) states, we determined placental production of ADM and ADM regulation by cytokines. Isolated, purified cytotrophoblast cultures from normal (n=8) and PE (n=10) placentas were cultured for 3 days in the absence or presence of 10 ng/mL epidermal growth factor (EGF), 1 ng/mL transforming growth factor (TGF)-beta1, 10 ng/mL tumor necrosis factor (TNF)-alpha, or 100 U/mL interferon (IFN)-gamma. Cells were also cultured for 3 days in 10% fetal bovine serum for determination of syncytial formation by desmoplakin staining. Pieces of normal and PE placentas were snap-frozen for ADM mRNA measurement. Results showed that basal ADM production into culture medium by radioimmunoassay was significantly lower in PE placental cells. EGF significantly stimulated ADM production in normal trophoblasts but did not in PE placentas. None of the factors TNF-alpha, TGF-beta1, or IFN-gamma altered ADM secretion in either normal or PE placentas. ADM expression by Northern blot analysis demonstrated a 34.3+/-8.3% reduction in mRNA expression in PE placentas. Syncytialization, as assessed by desmoplakin-outlined syncytial units, was decreased in PE placentas (day 3: normal, 16.7+/-1.3%; PE, 5.5+/-2.0%; P