The placental mTOR-pathway: correlation with early growth trajectories following intrauterine growth restriction?
The placental mTOR-pathway: correlation with early growth trajectories following intrauterine growth restriction?
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DOI：
10.1017/s2040174415001154
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发表时间：
2015-08-01
影响因子：
1.7
通讯作者：
Rascher, W.
中科院分区：
文献类型：
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作者：
Fahlbusch, F. B.;Hartner, A.;Rascher, W.
特发性宫内生长受限（IUGR）是胎盘营养供应受损的结果。患有 IUGR 并表现出产后追赶性生长的新生儿在成年后患心血管和代谢并发症的风险更高。哺乳动物雷帕霉素靶点（mTOR）最近被证明具有胎盘营养传感器的功能。因此，我们确定了胎盘 mTOR 信号级联成员与出生后生长发育参数之间可能的相关性。通过 IUGR v. 匹配的适当胎龄 (AGA) 胎盘中的蛋白质印迹分析 mTOR 通路信号成分、Akt、AMP 激活蛋白激酶 α、mTOR、p70S6 激酶 1 和胰岛素受体底物 1 的蛋白表达和活性。此外，mTOR 在胎盘切片中进行了免疫组织化学染色。蛋白质印迹分析的数据与 1 岁时回顾性生长学随访数据相关。我们发现 IUGR 组在生命的第一年出现了显着的追赶性生长。通过免疫组织化学方法在多个胎盘区室中检测到 MTOR 及其激活形式。我们确定了胎盘 mTOR 通路信号成分与 IUGR 出生时和 1 岁时生长学数据的相关性。然而，对产后 IUGR 和 AGA 胎盘中 mTOR 通路成分的蛋白表达和磷酸化水平的分析并未揭示特征性变化。我们的研究结果表明，激活的 mTOR 水平与 IUGR 后的早期追赶性生长相关。然而，在 mTOR 连接处汇聚的信号的复杂性及其细胞分布模式似乎限制了其作为这种情况下生物标志物的潜力。
Idiopathic intrauterine growth restriction (IUGR) is a result of impaired placental nutrient supply. Newborns with IUGR exhibiting postnatal catch-up growth are of higher risk for cardiovascular and metabolic co-morbidities in adult life. Mammalian target of rapamycin (mTOR) was recently shown to function as a placental nutrient sensor. Thus, we determined possible correlations of members of the placental mTOR signaling cascade with auxologic parameters of postnatal growth. The protein expression and activity of mTOR-pathway signaling components, Akt, AMP-activated protein kinase alpha, mTOR, p70S6kinase1 and insulin receptor substrate-1 were analysed via western blotting in IUGR v. matched appropriate-for-gestational age (AGA) placentas. Moreover, mTOR was immunohistochemically stained in placental sections. Data from western blot analyses were correlated with retrospective auxological follow-up data at 1 year of age. We found significant catch-up growth in the 1st year of life in the IUGR group. MTOR and its activated form are immunohistochemically detected in multiple placental compartments. We identified correlations of placental mTOR-pathway signaling components to auxological data at birth and at 1 year of life in IUGR. Analysis of the protein expression and phosphorylation level of mTOR-pathway components in IUGR and AGA placentas postpartum, however, did not reveal pathognomonic changes. Our findings suggest that the level of activated mTOR correlates with early catch-up growth following IUGR. However, the complexity of signals converging at the mTOR nexus and its cellular distribution pattern seem to limit its potential as biomarker in this setting.