Table 3. Pathways significantly correlated with telomere shortening in association with SLEs exposures.
| Pathway | Molecules | |
|---|---|---|
| 1 | Natural killer cell signaling | KIR3DL1, RRAS2, LAIR1, INPP5B, SYK, MAPK3, KIR3DL2, KIR2DL4, KIR3DL3 |
| 2 | Phosphatidylglycerol biosynthesis II | GPAM, LPCAT4, PTPMT1, AGPAT1 |
| 3 | Prostate cancer signaling | RRAS2, FOXO1, PA2G4, MAPK3, NFKBIE, NFKB2, GSTP1 |
| 4 | Ephrin B signaling | GNAS, RGS3, MAPK3, GNAO1, ACP1, HNRNPK |
| 5 | CDP-diacylglycerol biosynthesis I | GPAM, LPCAT4, AGPAT1 |
| 6 | MIF-mediated glucocorticoid regulation | MAPK3, NFKBIE, CD14, NFKB2 |
| 7 | Triacylglycerol biosynthesis | GPAM, LPCAT4, AGPAT1, PLPP1 |
| 8 | Role of NFAT in regulation of the immune response | GNAS, RRAS2, SYK, MAPK3, NFKBIE, GNAO1, MS4A2, MEF2A, NFKB2 |
| 9 | Crosstalk between dendritic cells and natural killer cells | KIR3DL1, FSCN1, KIR3DL2, NFKB2, KIR2DL4, KIR3DL3 |
| 10 | IL-1 signaling | IL1A, GNAS, NFKBIE, GNAO1, NFKB2, IRAK2 |
| 11 | MIF regulation of innate immunity | MAPK3, NFKBIE, CD14, NFKB2 |
| 12 | iNOS signaling | NFKBIE, CD14, NFKB2, IRAK2 |
| 13 | LPS-stimulated MAPK signaling | RRAS2, MAPK3, NFKBIE, CD14, NFKB2 |
| 14 | D-myo-inositol (1,4,5)-trisphosphate biosynthesis | PIP4K2B, PI4K2B, PLCH1 |
| 15 | TNFR1 signaling | NAIP, CRADD, NFKBIE, NFKB2 |
| 16 | PDGF signaling | RRAS2, ABL2, INPP5B, MAPK3, ACP1 |
| 17 | fMLP signaling in neutrophils | ACTR2, GNAS, RRAS2, MAPK3, NFKBIE, NFKB2 |
| 18 | Ephrin receptor signaling | ACTR2, GNAS, RGS3, RRAS2, PTPN13, MAPK3, GNAO1, ACP1 |
| 19 | TNFR2 signaling | NAIP, NFKBIE, NFKB2 |
| 20 | Glutathione-mediated detoxification | HPGDS, ANPEP, GSTP1 |
| 21 | PPARα/RXRα activation | GNAS, RRAS2, PRKAB1, MAPK3, NFKBIE, CYP2C18, NFKB2, ACVR1C |
| 22 | Epithelial adherens junction signaling | EPN2, ACTR2, RRAS2, LMO7, TUBB4A, ACVR1C, FARP2 |
| 23 | Histamine biosynthesis | HDC |
| 24 | Alanine biosynthesis III | NFS1 |
| 25 | 4-1BB signaling in T lymphocytes | MAPK3, NFKBIE, NFKB2 |
| 26 | IL-6 signaling | IL1A, RRAS2, MAPK3, NFKBIE, CD14, NFKB2 |
| 27 | Choline biosynthesis III | PLD3, PHKA1 |
| 28 | Apoptosis signaling | NAIP, RRAS2, MAPK3, NFKBIE, NFKB2 |
| 29 | TWEAK signaling | NAIP, NFKBIE, NFKB2 |
| 30 | PI3K/AKT signaling | RRAS2, FOXO1, INPP5B, MAPK3, NFKBIE, NFKB2 |
| 31 | IL-17A signaling in fibroblasts | MAPK3, NFKBIE, NFKB2 |
| 32 | PPAR signaling | IL1A, RRAS2, MAPK3, NFKBIE, NFKB2 |
| 33 | Superpathway of inositol phosphate compounds | ATP1A1, PTPN13, NUDT9, INPP5B, PIP4K2B, ACP1, PI4K2B, PLCH1 |
| 34 | IL-15 signaling | RRAS2, SYK, MAPK3, NFKB2 |
| 35 | Role of PI3K/AKT signaling in the pathogenesis of influenza | IFNA8, MAPK3, NFKBIE, NFKB2 |
| 36 | Hepatic cholestasis | IL1A, GNAS, ABCC2, NFKBIE, CD14, NFKB2, IRAK2 |
| 37 | Eicosanoid signaling | PTGFR, DPEP3, ALOX5AP, HPGDS |
| 38 | Phospholipase C signaling | ARHGEF5, GNAS, PLD3, RRAS2, SYK, MAPK3, MEF2A, NFKB2, RHOH |
| 39 | Angiopoietin signaling | RRAS2, FOXO1, NFKBIE, NFKB2 |
| 40 | Erythropoietin signaling | RRAS2, MAPK3, NFKBIE, NFKB2 |
| 41 | Insulin receptor signaling | RRAS2, FOXO1, TRIP10, INPP5B, MAPK3, ASIC3 |
| 42 | Antioxidant action of vitamin C | PLD3, MAPK3, NFKBIE, NFKB2, SLC2A3 |
| 43 | IL-10 signaling | IL1A, NFKBIE, CD14, NFKB2 |
| 44 | Spermine biosynthesis | SMS |
| 45 | Cardiolipin biosynthesis II | PTPMT1 |
| 46 | Putrescine biosynthesis III | AZIN2 |
| 47 | Cholecystokinin/gastrin-mediated signaling | IL1A, RRAS2, MAPK3, MEF2A, RHOH |
| 48 | Small cell lung cancer signaling | PA2G4, NFKBIE, NFKB2, SKP2 |
| 49 | PEDF signaling | RRAS2, MAPK3, NFKBIE, NFKB2 |
| 50 | B-cell receptor signaling | RRAS2, FOXO1, INPP5B, SYK, MAPK3, NFKBIE, NFKB2 |
| 51 | Rac signaling | ACTR2, RRAS2, MAPK3, PIP4K2B, NFKB2 |
| 52 | Role of RIG1-like receptors in antiviral innate immunity | IFNA8, NFKBIE, NFKB2 |
| 53 | Systemic lupus erythematosus signaling | IL1A, RRAS2, IFNA8, PRPF3, MAPK3, SNRPB2, PRPF6, SNRPE |
| 54 | NF-KB activation by viruses | RRAS2, MAPK3, NFKBIE, NFKB2 |
| 55 | Toll-like receptor signaling | IL1A, CD14, NFKB2, IRAK2 |
| 56 | Fc epsilon RI signaling | RRAS2, INPP5B, SYK, MAPK3, MS4A2 |
Abbreviations: IL, interleukin; SLE, stressful life events. All the 56 pathways from Ingenuity pathway analysis, using as input gene set the 405 genes significantly correlated between telomere shortening and SLEs (P-value<0.05).