Abnormal expression of transcription factor activator protein-2α in pathologic placentas.
Abnormal expression of transcription factor activator protein-2α in pathologic placentas.
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DOI：
10.1016/j.humpath.2012.01.011
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发表时间：
2012-11
期刊：
影响因子：
3.3
通讯作者：
Handwerger, Stuart
中科院分区：
文献类型：
--
作者：
Sheridan, Rachel M.;Stanek, Jerzy;Khoury, Jane;Handwerger, Stuart
本实验室最近的研究表明，转录因子AP-2α在人绒毛细胞滋养层细胞（CTB）向合体滋养层细胞（STB）分化过程中起着关键作用。然而，AP-2α在病理妊娠胎盘中的表达知之甚少。本研究比较了AP-2α在高危妊娠胎盘和胎龄匹配对照胎盘中的表达。分别取轻度子痫前期（PE）、重度PE、糖尿病（DM）、慢性高血压（HTN）、胎儿生长受限（FGR）各10例，正常对照组10例，取胎盘中央旁组织行AP-2α和E-cadherin双染色。由两名对疾病状态不知情的病理学家在每个胎盘的10个代表性40 x视野（HPF）中计数CTB和STB的总数以及这两种细胞类型中AP-2α阳性和阴性细胞核的数量。在大多数病理妊娠中，异常胎盘成熟的证据是STB与CTB的比值降低了1.5-1.7倍。AP-2α在STB中的表达在轻度PE、DM、HTN和FGR中较低（每种情况下p<0.0001），在重度PE中高出2倍，尽管这种增加没有统计学意义（p=0.3）。由于AP-2α已被证明是绒毛CTB分化的关键，我们的研究结果表明，转录因子和/或信号分子的AP-2α级联的异常可能有助于某些类型的高危妊娠中胎盘异常成熟的发病机制。AP-2α在轻度和重度PE中表达的不同模式清楚地表明这些疾病可能有两种独立的致病机制。
Recent studies from our laboratory have indicated that the transcription factor AP-2α plays a critical role in the differentiation of human villous cytotrophoblast cells (CTB) to syncytiotrophoblast cells (STB). However, little is known about the expression of AP-2α in placentas from pathologic pregnancies. This study compares the expression of AP-2α in placentas from high-risk pregnancies to gestational age-matched controls. Paracentral sections from grossly unremarkable areas of 10 placentas from each group of pregnancies complicated by mild preeclampsia (PE), severe PE, diabetes mellitus (DM), chronic hypertension (HTN), fetal growth restriction (FGR) and 10 control cases of placentas from normal pregnancies matched for gestational age (CG) were double immunostained for AP-2α and E-cadherin. The total numbers of CTB and STB and the numbers of AP-2α positive and negative nuclei in both of these cell types were counted by two pathologists blinded to disease status, in ten representative 40x fields (HPF) for each placenta. Abnormal placental maturation in most of pathologic pregnancies was evidenced by a 1.5–1.7-fold lower STB to CTB ratio. AP-2α expression in STB was lower in mild PE, DM, HTN and FGR (p<0.0001 in each instance) and was higher by 2-fold in severe PE, though this increase was not statistically significant (p=0.3). Since AP-2α has been shown to be critical for villous CTB differentiation, our findings suggest that abnormalities in the AP-2α cascade of transcription factors and/or signaling molecules may contribute to the pathogenesis of the abnormal maturation in placentas in certain types of high-risk pregnancies. The different pattern of AP-2α expression in mild and severe PE clearly suggests that these conditions may have two independent pathogenic mechanisms.
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影响因子：
3.8
作者：
Cross, JC
通讯作者：
Cross, JC
影响因子：
3.8
作者：
Mayhew, T. M.;Manwani, R.;Baker, P. N.
通讯作者：
Baker, P. N.
影响因子：
4.8
作者：
Piao, YS;Peltoketo, H;Vihko, R
通讯作者：
Vihko, R
DOI：
10.1111/j.1471-0528.2004.00071.x
发表时间：
2004-04-01
影响因子：
5.8
作者：
Vatten, LJ;Skjærven, R
通讯作者：
Skjærven, R
影响因子：
56.9
作者：
Genbacev, O;Zhou, Y;Fisher, SJ
通讯作者：
Fisher, SJ