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特发性膜性肾病(IMN)肾小球、肾小管和肾间质的蛋白质组学分析:一项统计学观察性研究。

Proteomic analysis of glomeruli, tubules and renal interstitium in idiopathic membranous nephropathy (IMN): A statistically observational study.

机构信息

The Organ Transplantation Department of No.924 Hospital of PLA Joint Logistic Support Force, Medical quality specialty of the Joint Logistic Support Force, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin, Guangxi, P.R. China.

The Second Department of Urology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, P.R. China.

出版信息

Medicine (Baltimore). 2023 Dec 15;102(50):e36476. doi: 10.1097/MD.0000000000036476.

Abstract

Idiopathic membranous nephropathy (IMN) is a common type of primary glomerulonephritis, which pathogenesis are highly involved protein and immune regulation. Therefore, we investigated protein expression in different microregions of the IMN kidney tissue. We used laser capture microdissection and mass spectrometry to identify the proteins in the kidney tissue. Using MSstats software to identify the differently expressed protein (DEP). Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to predict and enrich the potential functions of the DEPs, and DEPs were compared to the Public data in the gene expression omnibus (GEO) database for screening biomarkers of IMN. Immune infiltration analysis was used to analyze the immune proportion in IMN. Three significantly up-regulated proteins were identified in the glomeruli of patients with IMN; 9 significantly up-regulated and 6 significantly down-regulated proteins were identified in the interstitium of patients with IMN. Gene ontology analysis showed that the DEPs in the glomerulus and interstitium were mostly enriched in "biological regulation, the immune system, and metabolic processes." Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEPs in the glomerulus and interstitium were mostly enriched in the "immune system" and the "complement and coagulation cascades. " According to the public information of the GEO database, DEPs in our study, Coatomer subunit delta Archain 1, Laminin subunit alpha-5, and Galectin-1 were highly expressed in the IMN samples from the GEO database; in the immune infiltration analysis, the proportion of resting memory CD4 T cells and activated NK cells in IMN were significantly higher than in the normal group. This study confirmed that there were significant differences in protein expression in different micro-regions of patients with IMN, The protein Coatomer subunit delta Archain 1, Laminin subunit alpha 5, Galectin-1 are potential biomarkers of IMN, the memory T cells CD4 and NK cells, maybe involved in the immunologic mechanism in the development of IMN.

摘要

特发性膜性肾病(IMN)是一种常见的原发性肾小球肾炎,其发病机制高度涉及蛋白质和免疫调节。因此,我们研究了 IMN 肾组织不同微区的蛋白质表达。我们使用激光捕获显微切割和质谱法鉴定肾组织中的蛋白质。使用 MSstats 软件鉴定差异表达蛋白(DEP)。GO 分析和京都基因与基因组百科全书(KEGG)通路分析用于预测和富集 DEPs 的潜在功能,并将 DEPs 与基因表达综合数据库(GEO)公共数据库中的数据进行比较,以筛选 IMN 的生物标志物。免疫浸润分析用于分析 IMN 中的免疫比例。在 IMN 患者的肾小球中鉴定出 3 个明显上调的蛋白质;在 IMN 患者的间质中鉴定出 9 个明显上调和 6 个明显下调的蛋白质。GO 分析表明,肾小球和间质中的 DEPs 主要富集在“生物调节、免疫系统和代谢过程”。KEGG 分析表明,肾小球和间质中的 DEPs 主要富集在“免疫系统”和“补体和凝血级联”。根据 GEO 数据库的公共信息,我们研究中的 DEPs,衣壳蛋白亚基 delta 链 Archain 1、层粘连蛋白亚基 alpha-5 和半乳糖凝集素-1 在 GEO 数据库中的 IMN 样本中高表达;在免疫浸润分析中,IMN 中静止记忆 CD4 T 细胞和活化 NK 细胞的比例明显高于正常组。这项研究证实,IMN 患者不同微区的蛋白质表达存在显著差异,蛋白质衣壳蛋白亚基 delta 链 Archain 1、层粘连蛋白亚基 alpha-5、半乳糖凝集素-1 是 IMN 的潜在生物标志物,记忆性 T 细胞 CD4 和 NK 细胞可能参与了 IMN 发展中的免疫机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b193/10727647/d343a76c28a2/medi-102-e36476-g001.jpg

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