Peptidome profiling of umbilical cord plasma associated with gestational diabetes-induced fetal macrosomia
Peptidome profiling of umbilical cord plasma associated with gestational diabetes-induced fetal macrosomia
复制标题
与妊娠糖尿病引起的巨大胎儿相关的脐带血浆的肽组分析。
DOI：
10.1016/j.jprot.2016.03.001
复制
发表时间：
2016-04-29
影响因子：
3.3
通讯作者：
Shi, Zhonghua
中科院分区：
文献类型：
--
作者：
Liu, Fei;Zhao, Chun;Shi, Zhonghua
巨大胎儿，定义为出生体重>= 4000 g，可能影响15 - 45%的妊娠期糖尿病（GDM）妇女的新生儿。内源性肽与妊娠期糖尿病诱导的巨大儿之间的关联尚未通过肽组分析进行广泛研究。在这里，我们分析了脐带血浆结合超滤，使用分子量截止过滤器和液相色谱-串联质谱（LC-MS/MS），以调查GDM与巨大儿的潜在关联。由于巨体婴儿在以后的生活中对肥胖，糖尿病和心血管疾病的易感性增加，我们还旨在确定特定的生物标志物来检测这些未来的疾病。将30对GDM母亲和对照随机分为3个亚组。我们鉴定了235个肽，分子量在1000 - 3000 Da之间，来自115种蛋白质。裂解位点分析表明，这些肽在调节中被裂解，这可能反映了蛋白酶的活性和在脐带血浆中的分布。与对照组相比，GDM巨大儿组中2471.7、1077.2、1446.5和2372.7 Da的四种鉴定的肽显著差异表达，其前体可能在GDM巨大儿的发展中起关键作用。我们提供了第一次验证GDM巨大的肽组配置文件，并确定潜在的生物标志物连接的巨大的影响，以后的生活diseases.Biological意义：胎儿巨大是妊娠期糖尿病（GDM），这是一个常见的医疗条件在怀孕期间的主要不良后果。目前，妊娠期糖尿病导致巨大儿的分子机制尚不清楚。由于肽组技术的高检测灵敏度和高通量，现在可以系统地鉴定可能涉及GDM诱导的巨大儿病例的脐带血浆中的肽。利用基于LC-MS/MS的定量，我们总共鉴定了来自115个前体蛋白的235个肽。GDM组与对照组差异表达的4个多肽分子量分别为2471.7、1077.2、1446.5和2372.7Da。1077.2 Da的前体蛋白是纤维蛋白原α链（FGA），其也在Ai et al.1291研究中以GDM病例血清样品中下调的方式鉴定。进一步分析所鉴定的肽的切割模式揭示了组织中的酶根据其规则切割蛋白质。因此，这种定量的肽组方法可以识别相关的肽，可能在妊娠期糖尿病诱导的巨大儿中发挥作用，并给出有助于巨大儿后期疾病发展的候选生物标志物。(C)© 2016 Elsevier B.V.版权所有。
Fetal macrosomia, defined as a birth weight >= 4000 g, may affect 15-45% of newborns of women with gestational diabetes mellitus (GDM). The associations between endogenous peptides and gestational diabetes-induced macrosomia have not been investigated extensively by peptidome analysis. Here, we analyzed the umbilical cord plasma by combining ultrafiltration using molecular weight cut-off filters and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate potential associations of GDM with macrosomia. As macrosomic babies have increased susceptibility to obesity, diabetes and cardiovascular diseases in later life, we also aimed to identify-specific biomarkers to detect these future diseases. Thirty pairs of GDM mothers and controls were randomly divided into three subgroups. We identified 235 peptides of around 1000-3000 Da, originating from 115 proteins. Analyzing the cleavage sites revealed that these peptides were cleaved in regulation, which may reflect the protease activity and distribution in umbilical cord plasma. Four identified peptides, of 2471.7, 1077.2, 1446.5 and 2372.7 Da, were significantly differentially expressed in the GDM macrosomia groups compared with controls, whose precursors may play a critical role in developing GDM macrosomia. We provide for the first time a validated GDM macrosomia peptidome profile and identify potential biomarkers linking the effects of macrosomia to later-life diseases.Biological significance: Fetal macrosomia is the predominant adverse outcome of gestational diabetes mellitus (GDM), which is a frequent medical condition during pregnancy. Till now, the detailed molecular mechanisms underlying gestational diabetes-induced macrosomia are still not elucidated. With high detection sensitivity and high throughput of peptidome technology, it is now possible to systemically identify peptides possibly involved in the umbilical cord plasma of GDM induced macrosomia cases. With LC-MS/MS based quantification, totally, we identified 235 peptides originated from 115 precursor proteins. And four peptides of 2471.7, 1077.2, 1446.5 and 2372.7 Da differentially expressed between GDM cases and compared controls. A precursor protein of 1077.2 Da was fibrinogen alpha chain (FGA), which was also identified in the Ai et al. 1291 study with a downregulated manner in the serum samples of GDM cases. And further analysis the cleavage pattern of the identified peptides revealed that the enzymes in tissues cleaved the protein according to their rules. Thus, this quantitative peptidome approach can identify related peptides that may play a role in the gestational diabetes-induced macrosomia, and give candidate biomarkers contributing to the development of later-life diseases in macrosomic babies. (C) 2016 Elsevier B.V. All rights reserved.