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识别与系统性硬化症相关间质性肺病患者中 Tregs 相关基因的分子特征。

Identification of Tregs-Related Genes with Molecular Patterns in Patients with Systemic Sclerosis Related to ILD.

机构信息

Department of Rheumatology and Clinical Immunology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330000, China.

Medical College of Nanchang University, Nanchang 330000, China.

出版信息

Biomolecules. 2023 Mar 15;13(3):535. doi: 10.3390/biom13030535.

Abstract

BACKGROUND

Systemic Sclerosis (SSc) is an autoimmune disease that is characterized by vasculopathy, digital ulcers, Raynaud's phenomenon, renal failure, pulmonary arterial hypertension, and fibrosis. Regulatory T (Treg) cell subsets have recently been found to play crucial roles in SSc with interstitial lung disease (ILD) pathogenesis. This study investigates the molecular mechanism of Treg-related genes in SSc patients through bioinformatic analyses.

METHODS

The GSE181228 dataset of SSc was used in this study. CIBERSORT was used for assessing the category and proportions of immune cells in SSc. Random forest and least absolute shrinkage and selection operator (LASSO) regression analysis were used to select the hub Treg-related genes.

RESULTS

Through bioinformatic analyses, LIPN and CLEC4D were selected as hub Treg-regulated genes. The diagnostic power of the two genes separately for SSc was 0.824 and 0.826. LIPN was associated with the pathway of aminoacyl-tRNA biosynthesis, Primary immunodeficiency, DNA replication, etc. The expression of CLEC4D was associated with the pathway of Neutrophil extracellular trap formation, PPAR signaling pathway, Staphylococcus aureus infection, Systemic lupus erythematosus, TNF signaling pathway, and Toll-like receptor signaling pathway.

CONCLUSION

Through bioinformatic analyses, we identified two Treg-related hub genes (LIPN, CLEC4D) that are mainly involved in the immune response and metabolism of Tregs in SSc with ILD. Moreover, our findings may provide the potential for studying the molecular mechanism of SSc with ILD.

摘要

背景

系统性硬化症(SSc)是一种自身免疫性疾病,其特征为血管病变、指端溃疡、雷诺现象、肾衰竭、肺动脉高压和纤维化。最近发现调节性 T(Treg)细胞亚群在伴有间质性肺病(ILD)发病机制的 SSc 中发挥关键作用。本研究通过生物信息学分析研究 SSc 患者 Treg 相关基因的分子机制。

方法

本研究使用了 SSc 的 GSE181228 数据集。CIBERSORT 用于评估 SSc 中免疫细胞的类别和比例。随机森林和最小绝对值收缩和选择算子(LASSO)回归分析用于选择枢纽 Treg 相关基因。

结果

通过生物信息学分析,选择 LIPN 和 CLEC4D 作为枢纽 Treg 调控基因。这两个基因单独诊断 SSc 的能力分别为 0.824 和 0.826。LIPN 与氨酰-tRNA 生物合成途径、原发性免疫缺陷、DNA 复制等有关。CLEC4D 的表达与中性粒细胞胞外诱捕形成途径、PPAR 信号通路、金黄色葡萄球菌感染、系统性红斑狼疮、TNF 信号通路和 Toll 样受体信号通路有关。

结论

通过生物信息学分析,我们确定了两个主要参与 SSc 伴有 ILD 的 Treg 免疫反应和代谢的 Treg 相关枢纽基因(LIPN、CLEC4D)。此外,我们的发现可能为研究 SSc 伴有 ILD 的分子机制提供了潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd8c/10046355/3569fd13ef59/biomolecules-13-00535-g001.jpg

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