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人胎盘神经营养因子及其受体的差异表达与抗细胞凋亡作用。

Differential expression and the anti-apoptotic effect of human placental neurotrophins and their receptors.

机构信息

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto, Japan.

出版信息

Placenta. 2011 Oct;32(10):737-44. doi: 10.1016/j.placenta.2011.07.001. Epub 2011 Aug 9.

DOI:10.1016/j.placenta.2011.07.001
PMID:21831423
Abstract

Neurotrophin (NT) is important in the survival, maintenance and differentiation of neuronal tissue, and functions in follicle maturation, tumor growth, angiogenesis and immunomodulation; however, the expression of NT and its receptors (NTR) in human placenta and their influence on fetal growth are unclear. Here we investigated the correlation of NT and NTR in human placenta with uterine environment and fetal growth. TrkB, a NTR, mRNA was expressed on decidual and villous tissue and increased with gestational age, localizing in the trophoblast layer and endothelium by immunohistochemistry. Villous TrkB mRNA was significantly increased in preeclampsia (PE) than in controls and was higher in the normotensive small for gestational age (SGA) placenta, although it was not significant. It was also significantly increased in the small twin of discordant twin pregnancies. Brain-derived neurotrophic factor (BDNF), the main ligand of TrkB, was expressed in membranous chorion and villous tissue and was significantly higher in maternal plasma in normotensive SGA and PE than in controls. TrkB mRNA expression was up-regulated on cultured villous tissue explants and on JEG-3, a choriocarcinoma cell line, by H(2)O(2) treatment. BDNF decreased apoptotic cells in H(2)O(2)-treated JEG-3, indicating that BDNF/TrkB signaling had anti-apoptotic effects against oxidative stress in JEG-3, suggesting a protective role of BDNF/TrkB in human villous tissue under unfavorable conditions in utero.

摘要

神经生长因子(NT)在神经元组织的存活、维持和分化中起着重要作用,它在卵泡成熟、肿瘤生长、血管生成和免疫调节中发挥作用;然而,NT 及其受体(NTR)在人胎盘中的表达及其对胎儿生长的影响尚不清楚。在这里,我们研究了人胎盘 NT 和 NTR 与子宫环境和胎儿生长的相关性。NTR 中的一种 TrkB 的 mRNA 在蜕膜和绒毛组织中表达,并随着胎龄的增加而增加,免疫组化定位在滋养层和内皮细胞中。子痫前期(PE)的绒毛组织 TrkB mRNA 明显高于对照组,且正常血压小胎龄(SGA)胎盘中的含量更高,尽管差异无统计学意义。在双胎妊娠中不匀称的小胎儿中,其含量也明显升高。TrkB 的主要配体脑源性神经营养因子(BDNF)在膜状绒毛膜和绒毛组织中表达,在正常血压 SGA 和 PE 的母体外周血血浆中显著高于对照组。H 2 O 2处理培养的绒毛组织外植体和绒毛癌细胞系 JEG-3 可上调 TrkB mRNA 表达。BDNF 减少了 H 2 O 2 处理的 JEG-3 中的凋亡细胞,表明 BDNF/TrkB 信号在 JEG-3 中对氧化应激具有抗凋亡作用,提示 BDNF/TrkB 在人绒毛组织中的保护作用不利宫内条件。

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