Fig. 7: Bulk transcriptome analysis of dermatomyositis muscle biopsies and human myoblast culture with IFNγ suggest a causative link between this cytokine and mitochondrial dysfunction.
From: IFNγ causes mitochondrial dysfunction and oxidative stress in myositis
a Analysis of bulk transcriptomic data of muscle biopsies from 44 DM patients tested positive for myositis-specific autoantibodies against NXP2 (n = 14), TIF1γ (n = 12), Mi2 (n = 12), and MDA5 (n = 6), and from 33 histologically normal muscle biopsies focusing on mitochondrial genes (ATP8, ATP6, CO1, CO2, CO3, CYB, ND1, ND2, ND3, ND4, ND4L, ND5, and ND6). NT normal tissue, DM dermatomyositis. n corresponds to independent subjects. Box plots bounds to 25th to 75th percentiles, with line at the median, and whiskers correspond to 1.5 times the interquantile range (1.5×[Q3-Q1]). b Correlation of the expression of these mitochondrial genes with IFNγ-induced genes (GBP2, IFI30, IFNG) and other genes related to myositis disease activity: immune (CD3E, CD4, CD8A, CD14, CD68, NCAM1), myofiber regenerative (MYOG, PAX7, MYH3, MYH8) and mature myofiber markers (ACTA1, MYH1, MYH2). c Effect of IFNγ (100 U/mL or 1000 U/mL) on mitochondrial gene expression in differentiating human skeletal muscle myoblasts (n = 2 wells/condition). Expression Trimmed Means of M values (TMM) of GBP2, IFI30, ATP8, ATP6, CO1, CO2, CO3, CYB, ND1, ND2, ND3, ND4, ND4L, ND5, and ND6. d Electron microscopy of myotubes treated with IFNγ and IFNγ + JAK inhibitors (ruxolitinib 1 µM or baricitinib 1 µM) (left, scale bar 1 µm). A zoomed insert on a representative mitochondrion is shown on the right (scale bar 0.2 µm). Images are representative of n = 3 wells/condition. For a, the Benjamini–Hochberg was used to adjust for multiple comparisons and p values are included in Supplementary Table 2. Source data are provided as a Source Data file.
