Detergent-Insoluble Proteome Analysis Revealed Aberrantly Aggregated Proteins in Human Preeclampsia Placentas.
Detergent-Insoluble Proteome Analysis Revealed Aberrantly Aggregated Proteins in Human Preeclampsia Placentas.
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洗涤剂不溶性蛋白质组分析揭示了人先兆子痫胎盘中异常聚集的蛋白质。
DOI：
10.1021/acs.jproteome.7b00352
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Wang Tong
中科院分区：
文献类型：
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作者：
Zhang Wanling;Chen Xing;Yan Ziqi;Chen Yang;Cui Yizhi;Chen Bingjun;Huang Chujun;Zhang Weiwen;Yin Xingfeng;He Qing-Yu;He Fang;Wang Tong
子痫前期（PE）是一种以高血压、蛋白尿和其他多器官功能障碍为特征的胎盘疾病，其病因尚不清楚。我们和其他人已经表明，内质网（ER）应激和未折叠蛋白反应（UPR）发生在PE胎盘中。在这项研究中，我们从人胎盘组织中分离出富含蛋白质聚集体的洗涤剂不溶性蛋白（DIPs），以表征PE中的胎盘UPR。通过数据独立采集（DIA）质谱分析，我们在所有正常（n= 10）和PE （n= 10）胎盘样本中鉴定出2066个dip，其中PE中110个和108个dip分别显著上调和下调。通过聚类分析，差异DIPs一般可以区分PE和正常胎盘。我们用免疫印迹法验证了内啡肽和波形蛋白的质谱定量。此外，我们观察到PE胎盘组织的细胞质中有明显更多的内啡肽。此外，我们发现DIPs在不同染色体上分布均匀，可以丰富多种基因本体术语，而差异DIPs避免分布在x染色体上。PE中显著上调的DIPs主要集中在脂质代谢的顶层功能，其中23个DIPs可以组成调控细胞运动、发育、生长和增殖的顶层网络。我们的结果表明，人类PE胎盘具有与疾病相关的差异DIPs，这反映了胎盘组织异常聚集的蛋白质。质谱蛋白质组学数据已存入ProteomeXchange联盟，数据集标识符为PXD006654， iProX数据库（登录号：IPX0000948000）。
Preeclampsia (PE) is a placenta disease, featured by hypertension, proteinuria, and other multiorgan dysfunctions, and its etiology is unclear. We and others have shown that intensive endoplasmic reticulum (ER) stress and unfolded protein response (UPR) occur in the PE placenta. In this study, we isolated detergent-insoluble proteins (DIPs) from human placenta tissues, which were enriched with protein aggregates, to characterize the placenta UPR in PE. With data-independent acquisition (DIA) mass spectrometry, we identified 2066 DIPs across all normal (n= 10) and PE (n= 10) placenta samples, among which 110 and 108 DIPs were significantly up- and down-regulated in PE, respectively. Per clustering analysis, differential DIPs could generally distinguish PE from normal placentas. We verified the MS quantitation of endoglin and vimentin by immunoblotting. In addition, we observed that PE placenta tissues have remarkably more endoglin in the cytoplasm. Furthermore, we found that DIPs were evenly distributed across different chromosomes and could be enriched in diversified gene ontology terms, while differential DIPs avoided to distribute on X-chromosome. Significantly up-regulated DIPs in PE were focused on the top functions of lipid metabolism, while 23 of these DIPs could form the top network regulating cellular movement, development, growth, and proliferation. Our results implicate that human PE placentas have disease-relevant differential DIPs, which reflect aberrantly aggregated proteins of placental tissues. The mass spectrometry proteomics data have been deposited to ProteomeXchange consortium with the data set identifier PXD006654, and iProX database (accession number: IPX0000948000).