Fig 1: Possible mechanisms of ITGA5, ITGB2, and ITGB5 involved in SSc. Top 10 significantly enriched GO terms for ITGA5 (A–C), ITGB2 (D–F), and ITGB5 (G–I). The size of the circle represents gene count. Different colors of circles represent different adjusted p-value. Gene ratio means the number of genes in ITGA5 and ITGB2/B5 co-expressed genes (r > 0.5); genes that belong to this pathway divided by the number of genes in the background gene cluster that belong to this pathway. GO, Gene Ontology; SSc, systemic sclerosis.
Fig 2: Correlation between aberrant expressed integrin family gene and the infiltration of immune and stromal cells in the skin of SSc. (B) The abundance of CD8+ T cell is relatively low in the skin from SSc patients than healthy controls. (F, I, J) The abundance of monocytic lineage, endothelial, and fibroblast were higher in SSc patients compared with healthy control, respectively. (A, C–E, G, H) The abundance of total T cells, cytotoxic lymphocytes, B cells, NK cells, myeloid dendritic cells, and neutrophils showed no difference between SSc patients and healthy control. (K) The mRNA expression level of ITGA5 was positively correlated with fibroblasts (r = 0.47, p < 0.0001), endothelial cells (r = 0.44, p < 0.0001), and monocytes (r = 0.35, p < 0.0001). The mRNA expression level of ITGB2 was significantly higher than that of fibroblasts (r = 0.64, p < 0.0001), endothelial cells (r = 0.52, p < 0.0001), T cells (r = 0.36, p < 0.0001), and myeloid dendritic cells (r = 0.39, p < 0.0001). The mRNA expression level of ITGB5 was positively correlated with fibroblasts (r = 0.63, p < 0.0001), endothelial cells (r = 0.43, p < 0.0001), and monocytes (r = 0.26, p = 0.0021). SSc, systemic sclerosis.
Fig 3: Correlation between aberrant expressed integrin family genes and clinical features of SSc from GSE58095. (A) The mRNA expression of ITGA5, ITGB2, and ITGB5 genes was positively correlated with mRSS, respectively. (B) The mRNA expression levels of ITGA5 and ITGB5 were higher in dcSSc than in lcSSc. (C) ITGB2 was downregulated in patients seropositive for ACA than in lacking specific antibodies. The gene expression of ITGB5 was higher in patients seropositive for ACA than in those lacking specific antibodies or those seropositive for either RNP or ATA. SSc, systemic sclerosis; dcSSc, diffused cutaneous systemic sclerosis; lcSSc, limited cutaneous systemic sclerosis; mRSS, modified Rodnan skin thickness score; RNP, anti-U1 RNP antibody; ACA, anti-centromere antibody; ATA, anti-topoisomerase antibody; RNAP, anti-RNA polymerase III antibody.
Fig 4: Top 10 significantly enriched KEGG pathway for ITGA5, ITGB2, and ITGB5 involved in SSc. (A) ITGA5; (B) ITGB2; (C) ITGB5. The red circle represents genes, and the blue circle represents related signaling pathways enriched by genes. KEGG, Kyoto Encyclopedia of Genes and Genomes; SSc, systemic sclerosis.
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