Project description:Post-translational modifications (PTMs) are considered to be an important factor in the pathogenesis of SLE. Lysine 2-hydroxyisobutyryl (Khib), as an emerging post-translational modification of proteins, is involved in some important biological metabolic activities. We compared the Khib levels of SLE patients and healthy controls based on liquid chromatography-tandem mass spectrometry, and then performed proteomic analysis. The results showed that Khib in SLE patients was up-regulated at 865 sites of 416 proteins and down-regulated at 630 sites of 349 proteins. The site abundance, distribution and function of Khib protein were further analyzed. Bioinformatics analysis showed that complement, coagulation cascade and platelet activation in immune-related pathways were significantly enriched, indicating that the differential modification proteins between them might affect SLE.
Project description:Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that displays a significant gender difference in terms of incidence and severity. However, the underlying mechanisms accounting for sexual dimorphism remain unclear. To reveal the heterogeneity in the pathogenesis of SLE between male and female patients. PBMC were collected from 15 patients with SLE (7 males, 8 females) and 15 age-matched healthy controls (7 males, 8 females) for proteomic analysis. Enrichment analysis of proteomic data revealed that type I interferon signaling and neutrophil activation networks mapped to both male and female SLE, while male SLE has a higher level of neutrophil activation compared with female SLE. Our findings define gender heterogeneity in the pathogenesis of SLE and may facilitate the development of gender-specific treatments.
Project description:To clarify the role of interferon regulatory factor 5 (IRF5) other than inducing type I interferons (IFNs) in the pathogenesis of systemic lupus erythematosus (SLE), we performed transcriptome analysis of peripheral blood from Lyn-deficient mice with concomitant Ifnar1 or Irf5 deficiency. The results of gene set enrichment analysis (GSEA) suggest that IRF5 is involved in the induction of not only IFN-inducible genes (ISGs) but also oxidative phosphorylation (OXPHOS)-related genes in the SLE pathogenesis.