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维生素D缺乏对免疫相关枢纽基因的影响:一项与1型糖尿病相关的网络分析

The Effect of Vitamin D Deficiency on Immune-Related Hub Genes: A Network Analysis Associated With Type 1 Diabetes.

作者信息

Hussein Safin, Bandarian Fatemeh, Salehi Najmeh, Mosadegh Khah Ali, Motevaseli Elahe, Azizi Zahra

机构信息

Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, IRN.

Biology, College of Science, University of Raparin, Ranya, IRQ.

出版信息

Cureus. 2024 Sep 4;16(9):e68611. doi: 10.7759/cureus.68611. eCollection 2024 Sep.

Abstract

Background Type 1 diabetes (T1D) is an autoimmune disorder that results in the destruction of pancreatic beta cells, causing a shortage of insulin secretion. The development of T1D is influenced by both genetic predisposition and environmental factors, such as vitamin D. This vitamin is known for its ability to regulate the immune system and has been associated with a decreased risk of T1D. However, the specific ways in which vitamin D affects immune regulation and the preservation of beta cells in T1D are not yet fully understood. Gaining a better understanding of these interactions is essential for identifying potential targets for preventing and treating T1D. Methods The analysis focused on two Gene Expression Omnibus (GEO) datasets, namely, GSE55098 and GSE50012, to detect differentially expressed genes (DEGs). Enrichr (Ma'ayan Laboratory, New York, NY) was used to perform enrichment analysis for the Gene Ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The Search Tool for the Retrieval of Interacting Genes 12.0 (STRING) database was used to generate a protein-protein interaction (PPI) network. The Cytoscape 3.10.1 (Cytoscape Team, San Diego, CA) was used to analyze the PPI network and discover the hub genes. Results The DEGs in both datasets were identified using the GEO2R tool, with a particular focus on genes exhibiting contrasting regulations. Enrichment analysis unveiled the participation of these oppositely regulated DEGs in processes relevant to the immune system. Cytoscape analysis of the PPI network revealed five hub genes, MNDA, LILRB2, FPR2, HCK, and FCGR2A, suggesting their potential role in the pathogenesis of T1D and the response to vitamin D. Conclusion The study elucidates the complex interaction between vitamin D metabolism and immune regulation in T1D. The identified hub genes provide important knowledge on the molecular pathways that underlie T1D and have the potential to be targeted for therapeutic intervention. This research underscores the importance of vitamin D in the immune system's modulation and its impact on T1D development.

摘要

背景 1 型糖尿病(T1D)是一种自身免疫性疾病,会导致胰腺β细胞被破坏,从而引起胰岛素分泌不足。T1D 的发展受遗传易感性和环境因素(如维生素 D)的影响。这种维生素以其调节免疫系统的能力而闻名,并且与 T1D 风险降低有关。然而,维生素 D 影响免疫调节以及 T1D 中β细胞保护的具体方式尚未完全了解。更好地理解这些相互作用对于确定预防和治疗 T1D 的潜在靶点至关重要。方法 该分析聚焦于两个基因表达综合数据库(GEO)数据集,即 GSE55098 和 GSE50012,以检测差异表达基因(DEG)。使用 Enrichr(纽约州纽约市马亚恩实验室)对基因本体论(GO)生物学过程和京都基因与基因组百科全书(KEGG)通路进行富集分析。使用检索相互作用基因的搜索工具 12.0(STRING)数据库生成蛋白质 - 蛋白质相互作用(PPI)网络。使用 Cytoscape 3.10.1(加利福尼亚州圣地亚哥市 Cytoscape 团队)分析 PPI 网络并发现枢纽基因。结果 使用 GEO2R 工具识别了两个数据集中的 DEG,特别关注表现出相反调节的基因。富集分析揭示了这些反向调节的 DEG 参与了与免疫系统相关的过程。对 PPI 网络的 Cytoscape 分析揭示了五个枢纽基因,即 MNDA、LILRB2、FPR2、HCK 和 FCGR2A,表明它们在 T1D 发病机制和对维生素 D 的反应中可能发挥的作用。结论 该研究阐明了 T1D 中维生素 D 代谢与免疫调节之间的复杂相互作用。所确定的枢纽基因提供了关于 T1D 潜在分子途径的重要知识,并且有可能成为治疗干预的靶点。这项研究强调了维生素 D 在调节免疫系统及其对 T1D 发展影响方面的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0060/11452324/dc5d063570a3/cureus-0016-00000068611-i01.jpg

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