CEBPA as a potential hub gene for cutaneous inflammation in type 2 diabetes mellitus.

IF 7.7 1区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY International Journal of Biological Macromolecules Pub Date : 2025-04-01 Epub Date: 2025-01-19 DOI:10.1016/j.ijbiomac.2025.140080

Mingzheng Han, Jingchun Wang, Yijin Wu, Jianzhao Liao, Jianying Guo, Zhaoxin Tang

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Abstract

Background: The role of inflammation in the development of type 2 diabetes mellitus (T2DM) related skin complications necessitates further investigation. This study aims to explore the correlation between inflammation and cutaneous alterations in T2DM, enhancing comprehension of underlying mechanism involved.

Methods: Utilizing bioinformatics, the GSE38396 and GSE92724 datasets were employed to identify differentially expressed genes (DEGs) and potential hub genes in T2DM-related skin inflammation. Subsequently, gene functional enrichment analysis was employed for functional annotation. Finally, we validated the regulatory impact of hub gene on inflammation during high glucose incubation using the in vitro model.

Results: A comprehensive analysis identified 742 DEGs, including 9 hub genes and 4 potential biomarkers. Compared to the CON group, the expression of M2 macrophages was significantly upregulated in the T2DM group, while resting dendritic cells and eosinophils showed notable decreases, indicating a significant correlation with CEBPA. Furthermore, functional enrichment analysis revealed significant enrichment of DEGs in pathways linked to immunity and diabetes pathogenesis. Interestingly, overexpression of CEBPA demonstrated anti-inflammatory effects under hyperglycemic conditions, while silencing CEBPA expression appeared to worsen inflammation.

Conclusion: CEBPA emerges as a potential hub gene for skin inflammation in T2DM, shedding light on the underlying mechanisms of this condition.

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CEBPA是2型糖尿病皮肤炎症的潜在中枢基因。

背景：炎症在2型糖尿病（T2DM）相关皮肤并发症发生中的作用需要进一步研究。本研究旨在探讨T2DM患者炎症与皮肤改变之间的关系，加深对其潜在机制的理解。方法：利用生物信息学方法，利用GSE38396和GSE92724数据集，鉴定t2dm相关皮肤炎症的差异表达基因（DEGs）和潜在枢纽基因。随后，利用基因功能富集分析进行功能注释。最后，我们通过体外模型验证了hub基因在高糖培养过程中对炎症的调节作用。结果：综合分析共鉴定出742个deg，包括9个枢纽基因和4个潜在的生物标志物。与CON组相比，T2DM组M2巨噬细胞表达明显上调，而静息树突状细胞和嗜酸性粒细胞表达明显降低，提示与CEBPA有显著相关性。此外，功能富集分析显示，deg在与免疫和糖尿病发病机制相关的途径中显著富集。有趣的是，在高血糖条件下，CEBPA的过表达显示出抗炎作用，而沉默CEBPA的表达似乎会加重炎症。结论：CEBPA是T2DM患者皮肤炎症的潜在中枢基因，揭示了T2DM的潜在机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Biological Macromolecules 生物-生化与分子生物学

CiteScore

13.70

自引率

9.80%

发文量

2728

审稿时长

64 days

期刊介绍： The International Journal of Biological Macromolecules is a well-established international journal dedicated to research on the chemical and biological aspects of natural macromolecules. Focusing on proteins, macromolecular carbohydrates, glycoproteins, proteoglycans, lignins, biological poly-acids, and nucleic acids, the journal presents the latest findings in molecular structure, properties, biological activities, interactions, modifications, and functional properties. Papers must offer new and novel insights, encompassing related model systems, structural conformational studies, theoretical developments, and analytical techniques. Each paper is required to primarily focus on at least one named biological macromolecule, reflected in the title, abstract, and text.