Phosphoproteomic profile of peripheral blood mononuclear cells in mesangial proliferative glomerulonephritis patients

Yangyyang Zhang, Guoping Sun, Feng-yan Li, Xiao-cong Lin, Wenbiao Chen, Y. Dai
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Abstract

To insight the pathogenesis of Mesangial proliferative glomerulonephritis (MsPGN), we investigated the phosphoproteomic profile of PBMCs from MsPGN patients and normal subjects by integrating TiO 2 enrichment technology, 2D nano-liter liquid chromatography and linear ion trap quadrupole mass spectrometry. We identified totally 693 differential phosphorylation sites and corresponded to 439 genes. Gene ontology (GO) analysis showed that protein or nucleic acid binding took up the largest proportion of molecular function, followed by nucleobase, nucleoside, nucleotide and nucleic acid metabolic process in the nucleus. KEGG Pathway analysis showed that most of differential gene enrich in mitogen-activated protein kinase (MAPK) signaling pathway and focal adhesion pathway. Gene network analysis showed that serine/arginine repetitive matrix (SRRM) 1, histone deacetylase (HDAC) 1 and protein kinase C delta (PRKED) were significantly regulators in the network. These results suggested that abnormal changes of protein phosphorylation modification may contribute to MsPGN, and may be derived from the dysregulation of MAPK signaling pathway and focal adhesion pathway. In these pathways, the differential genes SRRM1, HDAC1 and PRKCD with higher connection may be the promising biomarker for MsPGN.
系膜增生性肾小球肾炎患者外周血单个核细胞的磷酸化蛋白质组学分析
为了深入了解系膜增生性肾小球肾炎(MsPGN)的发病机制,我们采用tio2富集技术、二维纳米升液相色谱和线性离子阱四极杆质谱技术对MsPGN患者和正常人的ppbmcs进行了磷酸化蛋白质组学分析。共鉴定出693个差异磷酸化位点,对应439个基因。基因本体(Gene ontology, GO)分析显示,蛋白质或核酸结合在分子功能中所占比例最大,其次是核碱基、核苷、核苷酸和细胞核内的核酸代谢过程。KEGG通路分析显示,大部分差异基因富集于丝裂原活化蛋白激酶(MAPK)信号通路和局灶黏附通路。基因网络分析表明,丝氨酸/精氨酸重复基质(SRRM) 1、组蛋白去乙酰化酶(HDAC) 1和蛋白激酶C δ (PRKED)是该网络中的显著调节因子。这些结果表明,蛋白磷酸化修饰的异常变化可能导致MsPGN的发生,并可能源于MAPK信号通路和局灶黏附通路的失调。在这些途径中,连接度较高的差异基因SRRM1、HDAC1和PRKCD可能是MsPGN的有希望的生物标志物。
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