Comparative proteomic analysis of children FSGS FFPE tissues.
Comparative proteomic analysis of children FSGS FFPE tissues.
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儿童 FSGS FFPE 组织的比较蛋白质组学分析
DOI：
10.1186/s12887-022-03764-7
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发表时间：
2022-12-12
期刊：
影响因子：
2.4
通讯作者：
中科院分区：
文献类型：
--
作者：
在儿童中，局灶节段性肾小球硬化（FSGS）是类固醇抵抗性肾病综合征（SRNS）的主要原因。为了确定特异性候选物和类固醇抗性机制，我们通过液相色谱-串联质谱（LC-MS/MS）检测了福尔马林固定石蜡包埋（FFPE）肾组织蛋白谱。对7例激素敏感（SS）和11例激素耐药（SR）儿童FSGS患者进行肾脏活检。采用液相色谱-串联质谱法（LC-MS/MS）检测福尔马林固定石蜡包埋（FFPE）肾组织蛋白谱。进行了京都基因与基因组百科全书（KEGG）富集和基因本体（GO）分析，以及蛋白质-蛋白质相互作用（PPI）网络的构建。两种蛋白通过免疫组化染色在FSGS患者和小鼠模型中进一步验证。我们总共定量了4000多个蛋白，其中发现了325个SS组和SR组之间的差异表达蛋白（DEPs） （foldchange≥2，P<0.05）。氧化石墨烯的结果显示，最显著的上调蛋白主要与蛋白质运输、补体活化过程的调节和细胞溶解有关。此外，聚类分析显示两组在途径（溶酶体、补体末端途径）上存在差异。在这些候选基因中，对LAMP1和ACSL4进行了验证分析。LAMP1在肾小球中表达较高，而ACSL4在小管上皮细胞中表达较多。在这项研究中，确定了儿童FSGS患者类固醇抵抗的潜在机制和候选药物。这可能有助于确定儿童FSGS患者的潜在治疗靶点和预测这些蛋白质组学变化的结果。在线版本包含补充材料，可在10.1186/s12887-022-03764-7获得。
In children, focal segmental glomerulosclerosis (FSGS) is the main cause of steroid resistant nephrotic syndrome (SRNS). To identify specific candidates and the mechanism of steroid resistance, we examined the formalin-fixed paraffin embedded (FFPE) renal tissue protein profiles via liquid chromatography tandem mass spectrometry (LC-MS/MS). Renal biopsies from seven steroid-sensitive (SS) and eleven steroid-resistant (SR) children FSGS patients were obtained. We examined the formalin-fixed paraffin embedded (FFPE) renal tissue protein profiles via liquid chromatography tandem mass spectrometry (LC-MS/MS). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and Gene Ontology (GO) analysis, as well as the construction of protein-protein interaction (PPI) network were performed. Two proteins were further valiadated by immunohistochemistry staining in FSGS patients and mice models. In total, we quantified more than 4000 proteins, of which 325 were found to be differentially expressed proteins (DEPs) between the SS and SR group (foldchange ≥2, P<0.05). The results of GO revealed that the most significant up-regulated proteins were primarily related to protein transportation, regulation of the complement activation process and cytolysis. Moreover, clustering analysis showed differences in the pathways (lysosome, terminal pathway of complement) between the two groups. Among these potential candidates, validation analyses for LAMP1 and ACSL4 were conducted. LAMP1 was observed to have a higher expression in glomerulus, while ACSL4 was expressed more in tubular epithelial cells. In this study, the potential mechanism and candidates related to steroid resistance in children FSGS patients were identified. It could be helpful in identifying potential therapeutic targets and predicting outcomes with these proteomic changes for children FSGS patients. The online version contains supplementary material available at 10.1186/s12887-022-03764-7.
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