北京生物医学工程

基于GEO数据库挖掘与膜性肾病密切相关的关键基因

Identification of key genes associated with membranous nephropathy based on GEO database

作者：高燕李叶段雪婷王倩张海松李铭

单位：河北大学附属医院肾内科（河北保定  071000） 河北大学临床医学院（河北保定  071000） 河北省慢性肾脏病骨骼代谢生理学重点实验室（河北保定  071000） 河北大学基础医学院（河北保定  071000） 通信作者：李铭。E-mail: liming7654321@126.com

关键词： GEO数据库；膜性肾病；生物信息学分析；差异表达基因；信号通路

分类号：R318

出版年·卷·期（页码）：2022·41·2（118-124）

摘要：

目的膜性肾病是造成成年人肾病综合征的最常见因素之一，约1/3的患者会发展为终末期肾病。近年来，虽然与膜性肾病有关的自身抗原陆续被鉴定出来，但是对于其发病机制还是知之甚少。本研究依托GEO数据库的GSE108113数据集，从中提取膜性肾病患者的转录组相关数据，并通过生物信息学分析寻找与膜性肾病密切相关的关键基因和相关信号通路。方法首先通过R软件分析获取在正常人肾小球组织和膜性肾病病人肾小球组织之间差异表达的基因，最终获得36个上调差异表达基因和126个下调差异表达基因。然后对差异表达基因进行GO注释和KEGG通路分析，最后通过Cytoscape软件里的MCODE插件进行聚类分析筛选核心基因。结果通过生物信息学分析后最终获得以CYP3A5，CYP4A11，CYP2B6为代表的13个核心基因在正常肾小球与膜性肾病肾小球中差异表达，并且这些差异表达基因显著富集在药物代谢和视黄醇代谢通路。结论本研究揭示了与膜性肾病密切相关的13个关键基因和药物代谢等信号通路，为揭示膜性肾病的发病机制提供研究基础。

Objective Membranous nephropathy (MN) is a major cause of nephrotic syndrome in adults. Approximately one third of the MN patients will progress to end-stage renal disease. Although, the autoantigen related with MN has been identified in recent years, the underlying pathological mechanism of MN is still unclear. Methods In the present study, we obtained the transcriptomes data of MN patients from GSE108113 in GEO database, in order to identify core genes in relate with the formation of MN through bioinformatical analysis. We first got 36 up-regulated differentially expressed genes (DEGs) and 126 down-regulated DEGs, after gene expression profiling analysis by R software compared the healthy glomeruli with the glomeruli of MN patients. Then the gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis were carried out and the core genes were selected by the MCODE application of Cytoscape. Results The bioinformatical results illustrated that DEGs was significantly enriched in drug metabolism and retinol metabolism. Moreover, MCODE application picked up the 13 core genes represented by CYP3A5, CYP4A11, CYP2B6 differently expressed between the healthy and MN glomeruli. Conclusions Our research found 13 core genes and drug metabolism pathway which are connected with the development of MN, and will be benefit to uncover the pathological mechanism of MN.

参考文献：

[1] Ronco?P, Debiec H.?Molecular Pathogenesis of Membranous Nephropathy [J]. Annual Review of Pathology, 2020, 15: 287-313.

[2] Deegens JK, Wetzels JF. Membranous nephropathy in the older adult: epidemiology, diagnosis and management?[J]. Drugs and Aging, 2007, 24(9): 717-732.

[3] Bobkova IN, Kakhsurueva PA, Stavrovskaya EV. Idiopathic membranous nephropathy: Evolution in understanding the problem[J]. Terapevticheskii??Arkhiv, 2016, 88(6):89-94.

[4] Ronco P, Debiec H. Pathophysiological advances in membranous nephropathy: time for a shift in patient's care?[J]. The Lancet, 2015, 385(9981): 1983-1992.

[5] Francis JM, Beck LH Jr, Salant DJ. Membranous nephropathy: a journey from bench to bedside [J]. American Journal of Kidney Diseases,?2016, 68(1): 138-147.

[6] Tomas NM, Hoxha E, Reinicke AT, et al. Autoantibodies against thrombospondin type 1 domain-containing 7A induce membranous nephropathy [J]. The Journal of Clinical Investigation, 2016, 126(7):?2519-2532.

[7] Sinico RA,?Mezzina N, Trezzi B, et al. Immunology of membranous nephropathy: from animal models to humans [J]. Clinical and Experimental?Immunology, 2016, 183(2):?157-165.

[8] Segawa Y, Hisano S, Matsushita M, et al. IgG subclasses and complement pathway in segmental and global membranous nephropathy [J]. Pediatric Nephrology, 2010, 25(6): 1091-1099.

[9] Debiec H, Guigonis V, Mougenot B, et al. Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies [J]. The New England Journal of Medicine, 2002, 346(26): 2053-2060.

[10] Beck LH Jr, Bonegio RG, Lambeau G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy [J]. The New England Journal of Medicine, 2009, 361(1): 11-21.

[11] Tomas NM, Beck LH Jr, Meyer-Schwesinger C, et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy [J].?The New England Journal of Medicine, 2014, 371(24): 2277-2287.

[12] Rudnicki M, Perco P, D'Haene B, et al. Renal microRNA- and RNA-profiles in progressive chronic kidney disease [J]. European Journal of Clinical Investigation, 2016, 46(3): 213-226.

[13] Ju W, Nair V, Smith S, et al.?Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker?[J]. Science Translational Medicine, 2015, 7(316): 316ra193.

[14] Garantziotis P, Doumas SAP, Boletis I, et al. Gene expression as a guide to the development of novel therapies in primary glomerular diseases [J]. Journal of Clinical Medicine, 2021, 10(11):?2262.

[15] Pawluczyk IZA, Didangelos A, Barbour SJ, et al. Differential expression of microRNA miR-150-5p in IgA nephropathy as a potential mediator and marker of disease progression [J]. Kidney International, 2021, 99(5): 1127-1139.

[16] Yu G, Wang LG, Han Y,?et al. clusterProfiler: an R package for comparing biological themes among gene clusters [J]. OMICS: A Journal of Integrative Biology, 2012, 16(5): 284-287.

[17] Xu X, Wang G, Chen N, et al. Long-term exposure to air pollution and increased risk of membranous nephropathy in China [J]. Journal of the American Society of Nephrology, 2016, 27(12): 3739-3746.

[18] Déri MT, Kiss áF, Tóth K,?et al. End-stage renal disease reduces the expression of drug-metabolizing cytochrome P450s [J]. Pharmacological Reports, 2020, 72(6): 1695-1705.

[19] Kim S,?Kim SJ, Yoon HE,?et al. Fimasartan, a novel angiotensin-receptor blocker, protects against renal inflammation and fibrosis in mice with unilateral ureteral obstruction: the possible role of Nrf2 [J]. International Journal of Medical Sciences, 2015, 12(11): 891-904.

[20] Liu J, Yu X, Zhong S, et al. Hepatic and renal metabolism of genistein: an individual-based model to predict glucuronidation behavior of genistein in different organs [J]. Journal of Pharmaceutical and Biomedical Analysis, 2017, 139: 252-262.

[21] Cappelli C, Tellez A, Jara C, et al. The TGF-beta profibrotic cascade targets ecto-5'-nucleotidase gene in proximal tubule epithelial cells and is a traceable marker of progressive diabetic kidney disease [J]. Biochimica et Biophysica Acta(BBA)-?Molecular Basis of Disease, 2020, 1866(7): 165796.

[22]?Tang?S,?Wang?X,?Deng?T,?et?al.?Identification?of?C3?as?a?therapeutic?target?for?diabetic?nephropathy?by?bioinformatics?analysis?[J].?Scientific?Reports,?2020,10(1)：13468.

服务与反馈：

【文章下载】【加入收藏】

提示：您还未登录，请登录！点此登录