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1型糖尿病中维生素D诱导的免疫调节基因表达变化分析:从计算预测到实验验证

Analysis of vitamin D-induced immunomodulatory gene expression changes in type 1 diabetes: from computational prediction to experimental validation.

作者信息

Hussein Safin, Mahmoudi-Aznaveh Azam, Nekoeian Shahram, Qurbani Karzan, Panji Mohammad, Zakeri Pooya, Bandarian Fatemeh, Motevaseli Elahe, Azizi Zahra

机构信息

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

Department of Biology, College of Science, University of Raparin, Ranya, Kurdistan Region, Iraq.

出版信息

Mol Biol Rep. 2025 Sep 22;52(1):939. doi: 10.1007/s11033-025-11056-3.

Abstract

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the destruction of pancreatic beta cells. Vitamin D is known to have immunomodulatory effects that may influence T1DM; however, its impact on immune gene expression in T1DM patients remains unclear. This study aimed to explore the effects of vitamin D on immunomodulatory gene expression in T1DM patients through bioinformatics analysis and qRT‒PCR validation. Two microarray datasets (GSE55098 and GSE50012) were analyzed to identify differentially expressed genes (DEGs) in T1DM and vitamin D-treated samples. Enrichment analysis and protein‒protein interaction (PPI) network analysis were used to identify key immune genes. qRT‒PCR was then performed on peripheral blood mononuclear cells (PBMCs) from T1DM patients and healthy controls. The analysis revealed 100 DEGs shared between the two datasets, with 58 showing opposite regulation. Six key immunomodulatory genes (CD226, CD40, RSAD2, OAS3, PTGS2, and LAMP3) were identified. qRT‒PCR confirmed the significant dysregulation of these genes in T1DM patients. Vitamin D treatment led to the downregulation of most genes, except for LAMP3, whose expression remained unchanged. Vitamin D modulates the expression of key immune genes in T1DM, suggesting its potential as an adjunctive therapy. Future studies should validate these findings with larger cohorts and explore the long-term effects of vitamin D on immune regulation.

摘要

1型糖尿病(T1DM)是一种自身免疫性疾病,其特征是胰腺β细胞遭到破坏。已知维生素D具有免疫调节作用,可能会影响T1DM;然而,其对T1DM患者免疫基因表达的影响仍不清楚。本研究旨在通过生物信息学分析和qRT-PCR验证,探讨维生素D对T1DM患者免疫调节基因表达的影响。分析了两个微阵列数据集(GSE55098和GSE50012),以鉴定T1DM和维生素D处理样本中的差异表达基因(DEG)。采用富集分析和蛋白质-蛋白质相互作用(PPI)网络分析来鉴定关键免疫基因。然后对T1DM患者和健康对照的外周血单核细胞(PBMC)进行qRT-PCR。分析揭示了两个数据集之间共有的100个DEG,其中58个表现出相反的调控。鉴定出六个关键免疫调节基因(CD226、CD40、RSAD2、OAS3、PTGS2和LAMP3)。qRT-PCR证实了这些基因在T1DM患者中存在明显的失调。维生素D治疗导致大多数基因下调,除了LAMP3,其表达保持不变。维生素D可调节T1DM中关键免疫基因的表达,表明其作为辅助治疗的潜力。未来的研究应以更大的队列验证这些发现,并探索维生素D对免疫调节的长期影响。

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