Identification of placental nutrient transporters associated with intrauterine growth restriction and pre-eclampsia.
Identification of placental nutrient transporters associated with intrauterine growth restriction and pre-eclampsia.
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DOI：
10.1186/s12864-018-4518-z
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发表时间：
2018-03-02
期刊：
影响因子：
4.4
通讯作者：
Albrecht C
中科院分区：
文献类型：
--
作者：
Huang X;Anderle P;Hostettler L;Baumann MU;Surbek DV;Ontsouka EC;Albrecht C
胎儿宫内生长受限（IUGR）和先兆子痫（PE）等妊娠障碍是全球围产期结局不良的主要原因。这两种疾病都与母胎营养转移受损有关，但IUGR和PE的关键转运机制尚未完全阐明。在这项研究中，我们的目的是确定与IUGR/PE的经胎盘营养缺乏高度相关的膜转运蛋白。使用7个合格的微阵列数据集（来自Gene Expression Omnibus）进行差异表达营养转运蛋白鉴定的计算机模拟分析，包括对照和IUGR/PE胎盘样本。因此，434个基因中的46个被鉴定为潜在的感兴趣的靶标。它们参与胎儿提供氨基酸、碳水化合物、脂质、维生素和微量元素。通过使用用于检索相互作用基因的搜索工具将感兴趣的靶标聚类到底物特异性相互作用网络中。使用定量RT-PCR对来自临床上充分表征的IUGR/PE患者（IUGR，n = 8; PE，n = 5; PE+IUGR，n = 10）和对照（足月，n = 13;早产，n = 7）的胎盘进行随后的湿实验室验证，然后生成2D分层热图。然后应用Kruskal-Wallis检验进行统计学评价，以检测显著不同的表达模式，而散点图分析表明哪些转运蛋白主要受IUGR或PE影响，或同样受两种疾病影响。通过两种方法鉴定，通过蛋白质印迹法在蛋白质水平进一步研究了三个重叠靶点，SLC 7A 7、SLC 38 A5（氨基酸转运蛋白）和ABCA 1（胆固醇转运蛋白）。从疾病和对照胎盘中分离的总胎盘组织裂解物和膜组分中的蛋白质分析表明，IUGR/PE中这三种营养转运蛋白的功能活性改变。本研究结合生物信息学分析、分子生物学实验和数学建模，揭示了IUGR/PE营养转运蛋白表达的系统性改变。在46个最初靶向的转运蛋白中，根据IUGR和PE的严重程度和疾病特异性，进一步研究了3个显著调控的基因。氨基酸转运蛋白SLC 7A 7和SLC 38 A5在IUGR/PE和对照组间表达差异显著，且受两种疾病的调控。相反，ABCA 1可能在PE的发展中发挥独特的作用。本文的在线版本（10.1186/s12864-018-4518-z）包含补充材料，可供授权用户使用。
Gestational disorders such as intrauterine growth restriction (IUGR) and pre-eclampsia (PE) are main causes of poor perinatal outcomes worldwide. Both diseases are related with impaired materno-fetal nutrient transfer, but the crucial transport mechanisms underlying IUGR and PE are not fully elucidated. In this study, we aimed to identify membrane transporters highly associated with transplacental nutrient deficiencies in IUGR/PE. In silico analyses on the identification of differentially expressed nutrient transporters were conducted using seven eligible microarray datasets (from Gene Expression Omnibus), encompassing control and IUGR/PE placental samples. Thereby 46 out of 434 genes were identified as potentially interesting targets. They are involved in the fetal provision with amino acids, carbohydrates, lipids, vitamins and microelements. Targets of interest were clustered into a substrate-specific interaction network by using Search Tool for the Retrieval of Interacting Genes. The subsequent wet-lab validation was performed using quantitative RT-PCR on placentas from clinically well-characterized IUGR/PE patients (IUGR, n = 8; PE, n = 5; PE+IUGR, n = 10) and controls (term, n = 13; preterm, n = 7), followed by 2D-hierarchical heatmap generation. Statistical evaluation using Kruskal-Wallis tests was then applied to detect significantly different expression patterns, while scatter plot analysis indicated which transporters were predominantly influenced by IUGR or PE, or equally affected by both diseases. Identified by both methods, three overlapping targets, SLC7A7, SLC38A5 (amino acid transporters), and ABCA1 (cholesterol transporter), were further investigated at the protein level by western blotting. Protein analyses in total placental tissue lysates and membrane fractions isolated from disease and control placentas indicated an altered functional activity of those three nutrient transporters in IUGR/PE. Combining bioinformatic analysis, molecular biological experiments and mathematical diagramming, this study has demonstrated systematic alterations of nutrient transporter expressions in IUGR/PE. Among 46 initially targeted transporters, three significantly regulated genes were further investigated based on the severity and the disease specificity for IUGR and PE. Confirmed by mRNA and protein expression, the amino acid transporters SLC7A7 and SLC38A5 showed marked differences between controls and IUGR/PE and were regulated by both diseases. In contrast, ABCA1 may play an exclusive role in the development of PE. The online version of this article (10.1186/s12864-018-4518-z) contains supplementary material, which is available to authorized users.
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DOI：
10.1152/ajpcell.2000.278.6.c1162
发表时间：
2000-06-01
影响因子：
5.5
作者：
Ayuk, PTY;Sibley, CP;Glazier, JD
通讯作者：
Glazier, JD
影响因子：
5.5
作者：
Baumann, Marc U.;Zamudio, Stacy;Illsley, Nicholas P.
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影响因子：
3.8
作者：
Baumann, M.;Koerner, M.;Albrecht, C.
通讯作者：
Albrecht, C.
影响因子：
3.1
作者：
Aiko Y;Askew DJ;Aramaki S;Myoga M;Tomonaga C;Hachisuga T;Suga R;Kawamoto T;Tsuji M;Shibata E
通讯作者：
Shibata E
影响因子：
4.7
作者：
Burns, R.;O'Herlihy, C.;Smyth, P. P. A.
通讯作者：
Smyth, P. P. A.