Journal Article Epublish
PubMed: 40097571 DOI: 10.1038/s41598-025-93872-y
Exploring mitochondrial and ferroptotic mechanisms for systemic lupus erythematosus biomarker identification and therapy.
Sci Rep 15(1):9140
Authors: Yunfeng Dai, Jianwen Liu, Yongxing Lai, Fei Gao, He Lin, Li Zhang, Zhihan Chen
Affiliations
- Fujian Medical University Shengli Clinical Medical College, Fuzhou, 350000, China. Department of Rheumatology, Fuzhou University Affiliated Provincial Hospital, No.134 Dongjie, Fuzhou, 350000, China.
- Fujian Medical University Shengli Clinical Medical College, Fuzhou, 350000, China.
- Department of Rheumatology, Fuzhou University Affiliated Provincial Hospital, No.134 Dongjie, Fuzhou, 350000, China.
- Fujian Medical University Shengli Clinical Medical College, Fuzhou, 350000, China. Department of Nephrology, Fuzhou University Affiliated Provincial Hospital, No.134 Dongjie, Fuzhou, 350000, China.
- Fujian Medical University Shengli Clinical Medical College, Fuzhou, 350000, China. Department of Rheumatology, Fuzhou University Affiliated Provincial Hospital, No.134 Dongjie, Fuzhou, 350000, China.
Abstract
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with heterogeneous clinical manifestations. Understanding the molecular mechanisms of SLE is crucial for developing effective therapeutic strategies. This study downloaded microarray datasets from the Gene Expression Omnibus (GEO) database. Single-cell RNA sequencing (scRNA-seq) data was processed to identify 19 clusters and annotated five major cell types. Then we calculated mitochondrial-related genes (MRGs) and ferroptosis-related genes (FRGs) scores. FRGs scored the highest in Megakaryocytes, while MRGs scored the highest in B cells. By employing pseudotime analysis, cell-cell communication analysis, and Single-Cell Regulatory Network Inference and Clustering (SCENIC) analysis, we explored the heterogeneity of cells in SLE. Hub genes were identified using high-dimensional weighted correlation network analysis (hdWGNCA) and machine learning algorithms, leading to the development of a predictive diagnostic model with high predictive accuracy. Immune infiltration analysis revealed significant correlations between diagnostic biomarkers and various immune cells. Lastly, molecular docking studies suggested Doxorubicin may exert therapeutic effects by affecting these diagnostic biomarkers. This study offers new insights into the pathogenesis of SLE and provide valuable directions for future therapeutic research.
MeSH
Cells, Genes, Biomarkers, Lupus Erythematosus, Systemic, Natural Science Disciplines, Therapeutics