Palmitoylation Dynamics in Systemic Lupus Erythematosus: Multi-Omics Insights and Potential Therapeutic Implications

IF 2.4 4区医学 Q2 RHEUMATOLOGY

International Journal of Rheumatic Diseases Pub Date : 2025-07-04 DOI:10.1111/1756-185X.70346

Zeyu Liu, Yanggang Hong, Guo Hua, Zixi Li, Chunyan Hua, Sheng Gao

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引用次数: 0

Abstract

Objective

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by immune dysregulation. The role of palmitoylation in regulating immune responses and its contribution to SLE pathogenesis remains insufficiently understood.

Methods

We conducted a multi-omics analysis using the GSE61635 dataset to identify differentially expressed genes (DEGs) in SLE. Palmitoylation-related genes (PRGs) were identified through differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning models. Single-cell RNA sequencing (scRNA-seq) was used to assess immune cell dynamics, and Mendelian randomization (MR) was employed to explore causal relationships between metabolites and SLE.

Results

We identified 3946 DEGs and 13 key PRGs associated with palmitoylation in SLE. Four hub genes (ACSL1, ZDHHC12, GPX1, and DDHD2) were highlighted as potential biomarkers. Functional enrichment analysis revealed that these genes are involved in fatty acid metabolism and immune signaling. scRNA-seq analysis showed increased palmitoylation activity in neutrophils and cytotoxic T lymphocytes (CTLs) in SLE. MR analysis identified four phospholipids containing palmitic acid as causally linked to SLE.

Conclusion

This study identifies ACSL1 and ZDHHC12 as potential therapeutic targets for modulating palmitoylation and immune responses in SLE. Further research is required to validate these findings and explore their clinical implications for SLE treatment.

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系统性红斑狼疮的棕榈酰化动力学：多组学见解和潜在的治疗意义

目的：系统性红斑狼疮（SLE）是一种以免疫失调为特征的复杂自身免疫性疾病。棕榈酰化在调节免疫反应中的作用及其在SLE发病机制中的作用仍未得到充分的了解。方法使用GSE61635数据集进行多组学分析，以鉴定SLE中的差异表达基因（DEGs）。通过差异表达分析、加权基因共表达网络分析（WGCNA）和机器学习模型鉴定棕榈酰化相关基因（PRGs）。单细胞RNA测序（scRNA-seq）用于评估免疫细胞动力学，孟德尔随机化（MR）用于探索代谢物与SLE之间的因果关系。结果我们鉴定出3946个DEGs和13个关键的PRGs与SLE的棕榈酰化相关。四个中心基因（ACSL1, ZDHHC12， GPX1和DDHD2）被强调为潜在的生物标志物。功能富集分析显示这些基因参与脂肪酸代谢和免疫信号传导。scRNA-seq分析显示，SLE患者中性粒细胞和细胞毒性T淋巴细胞（ctl）棕榈酰化活性增加。磁共振分析确定了四种含有棕榈酸的磷脂与SLE有因果关系。结论本研究确定ACSL1和ZDHHC12是调节SLE中棕榈酰化和免疫反应的潜在治疗靶点。需要进一步的研究来验证这些发现并探索其对SLE治疗的临床意义。

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 Rheumatic Diseases RHEUMATOLOGY-

CiteScore

3.70

自引率

4.00%

发文量

362

审稿时长

1 months

期刊介绍： The International Journal of Rheumatic Diseases (formerly APLAR Journal of Rheumatology) is the official journal of the Asia Pacific League of Associations for Rheumatology. The Journal accepts original articles on clinical or experimental research pertinent to the rheumatic diseases, work on connective tissue diseases and other immune and allergic disorders. The acceptance criteria for all papers are the quality and originality of the research and its significance to our readership. Except where otherwise stated, manuscripts are peer reviewed by two anonymous reviewers and the Editor.