Table 11.
Toxicity-related pathways identified by Ingenuity in human keratinocytes treated with 20,23(OH)2D3 for 24 h. Nuclear receptors are marked in bold.
| Ingenuity Toxicity Lists | p-Value | Overlap (%) | Downregulated | No Change | Upregulated | No Overlap with Dataset |
|---|---|---|---|---|---|---|
| Aryl Hydrocarbon Receptor Signaling | 2.6 × 10−9 | 21.1 | 90/161 (56%) | 0/161 (0%) | 56/161 (35%) | 15/161 (9%) |
| Cholesterol Biosynthesis | 1.1 × 10−8 | 62.5 | 13/16 (81%) | 0/16 (0%) | 3/16 (19%) | 0/16 (0%) |
| Renal Necrosis/Cell Death | 1.9 × 10−7 | 13.2 | 228/501 (46%) | 0/501 (0%) | 255/501 (51%) | 18/501 (4%) |
| Primary Glomerulonephritis Biomarker Panel (Human) | 1.7 × 10−6 | 63.6 | 5/11 (45%) | 0/11 (0%) | 6/11 (55%) | 0/11 (0%) |
| p53 Signaling | 2.6 × 10−6 | 21.2 | 54/99 (55%) | 0/99 (0%) | 45/99 (45%) | 0/99 (0%) |
| VDR/RXR Activation | 1.5 × 10−5 | 21.8 | 26/78 (33%) | 0/78 (0%) | 51/78 (65%) | 1/78 (1%) |
| Liver Proliferation | 3.0 × 10−5 | 14.5 | 96/227 (42%) | 0/227 (0%) | 120/227 (53%) | 11/227 (5%) |
| Cardiac Hypertrophy | 5.1 × 10−5 | 12.2 | 176/401 (44%) | 0/401 (0%) | 202/401 (50%) | 23/401 (6%) |
| Liver Necrosis/Cell Death | 7.8 × 10−5 | 13.3 | 117/279 (42%) | 0/279 (0%) | 150/279 (54%) | 12/279 (4%) |
| Oxidative Stress | 0.000380189 | 21.1 | 39/57 (68%) | 0/57 (0%) | 17/57 (30%) | 1/57 (2%) |
| Mechanism of Gene Regulation by Peroxisome Proliferators via PPARα | 0.000645654 | 16.8 | 38/95 (40%) | 0/95 (0%) | 56/95 (59%) | 1/95 (1%) |
| Xenobiotic Metabolism Signaling | 0.000794328 | 11.6 | 152/336 (45%) | 0/336 (0%) | 142/336 (42%) | 42/336 (13%) |
| Increases Renal Proliferation | 0.002398833 | 13.9 | 68/137 (50%) | 0/137 (0%) | 62/137 (45%) | 7/137 (5%) |
| Fatty Acid Metabolism | 0.002398833 | 14.5 | 65/117 (56%) | 0/117 (0%) | 31/117 (26%) | 21/117 (18%) |
| Increases Liver Steatosis | 0.003890451 | 15.7 | 32/83 (39%) | 0/83 (0%) | 48/83 (58%) | 3/83 (4%) |
| Decreases Depolarization of Mitochondria and Mitochondrial Membrane | 0.004570882 | 25 | 18/24 (75%) | 0/24 (0%) | 5/24 (21%) | 1/24 (4%) |
| Cell Cycle: G1/S Checkpoint Regulation | 0.004677351 | 16.7 | 35/66 (53%) | 0/66 (0%) | 28/66 (42%) | 3/66 (5%) |