Table 3 List of pathways impacted by AgNPs or Ag+ and DEGs involved in the pathways
From: Toxicity of nano- and ionic silver to embryonic stem cells: a comparative toxicogenomic study
Ingenuity Canonical Pathways | AgNPs | Ag+ | ||
|---|---|---|---|---|
p value | Molecules | p value | Molecules | |
Embryonic development | ||||
 Transcriptional regulatory network in embryonic stem cells | 0.0005 | HAND1, L1CAM, FOXC1 | 0.0000 | HAND1, GATA6, L1CAM, EOMES, SKIL, HOXB1, FOXC1, GATA4 |
 Human embryonic stem cell pluripotency | 0.0178 | SMAD7, SMAD6, BMP5 | 0.0074 | BMP4, WNT3, BMP2, SMAD7, SMAD6, BMP5, FZD2 |
 Mouse embryonic stem cell pluripotency |  |  | 0.0002 | LIFR, MYC, ID1, ID2, BMP4, T, ID3, FZD2 |
 Role of NANOG in mammalian embryonic stem cell pluripotency |  |  | 0.0001 | LIFR, BMP4, T, WNT3, BMP2, GATA6, BMP5, FZD2, GATA4 |
 Embryonic stem cell differentiation into cardiac lineages |  |  | 0.0115 | T, GATA4 |
 Factors promoting cardiogenesis in vertebrates |  |  | 0.0045 | BMP4, WNT3, BMP2, BMP5, FZD2, GATA4 |
 Cardiomyocyte differentiation via BMP receptors | 0.0022 | SMAD6, BMP5 | 0.0000 | BMP4, BMP2, SMAD6, BMP5, GATA4 |
 Regulation of the epithelial–mesenchymal transition pathway | 0.0407 | FOXC2, FGF14, PARD6B | 0.0003 | ETS1, FOXC2, ID2, FGF10, WNT3, FGF14, PARD6B, FGF3, NOTCH1, FZD2, FGF19 |
 Hepatic fibrosis/hepatic stellate cell activation |  |  | 0.0010 | IGFBP4, COL4A1, FLT1, KLF6, SMAD7, LAMA1, BAMBI, IGFBP5, COL4A2, KDR |
 Axonal guidance signaling |  |  | 0.0000 | SLIT3, SHH, PAPPA, BMP4, WNT3, BMP2, UNC5B, L1CAM, HHIP, SLIT2, ROBO3, BMP5, NTN1, EFNB2, PRKAR2B, GLIS1, TUBB4A, FZD2, PTCH2, NRP1, UNC5C |
 BMP signaling pathway | 0.0034 | SMAD7, SMAD6, BMP5 | 0.0003 | BMP4, PRKAR2B, BMP2, SMAD7, SMAD6, BMP5, CHRD |
 ERK5 signaling |  |  | 0.0209 | MYC, RPS6KA6, SGK1, CREB3L4 |
 FGF signaling |  |  | 0.0141 | FGF10, FGF14, CREB3L4, FGF3, FGF19 |
 Netrin signaling |  |  | 0.0040 | PRKAR2B, UNC5B, NTN1, UNC5C |
 Notch signaling |  |  | 0.0004 | DLL1, LFNG, DLL3, HES7, NOTCH1 |
 RAR activation | 0.0427 | ALDH1A2, SMAD7, SMAD6 | 0.0148 | PRKAR2B, CYP26A1, BMP2, ALDH1A2, SMAD7, SMAD6, ADCY8, RBP1 |
 Sonic Hedgehog signaling |  |  | 0.0001 | SHH, PRKAR2B, GLIS1, HHIP, PTCH2 |
 TGF-β signaling | 0.0490 | SMAD7, SMAD6 |  |  |
 eNOS signaling | 0.0191 | Hspa1b, HSPA1A/HSPA1B, KDR | 0.0007 | PRKAR2B, FLT1, HSPA1A/HSPA1B, PRKAA2, AQP8, ADCY8, KDR, LPAR3, NOSTRIN |
 VEGF family ligand-receptor interactions | 0.0389 | KDR, NRP1 |  |  |
Metabolism | ||||
 Choline biosynthesis III | 0.0490 | HMOX1 |  |  |
 Corticotropin releasing hormone signaling |  |  | 0.0389 | SHH, PRKAR2B, CREB3L4, ADCY8, PTCH2 |
 FXR/RXR activation |  |  | 0.0200 | TTR, APOB, VTN, VLDLR, MTTP, FGF19 |
 Heme degradation | 0.0166 | HMOX1 |  |  |
 Histamine degradation | 0.0490 | ALDH1A2 |  |  |
 NAD biosynthesis II (from tryptophan) | 0.0490 | TDO2 |  |  |
 Retinoate biosynthesis I |  |  | 0.0174 | BMP2, ALDH1A2, RBP1 |
 Serotonin degradation | 0.0145 | UGT2B28, ALDH1A2 |  |  |
 Sulfate activation for sulfonation |  |  | 0.0331 | PAPSS2 |
 Tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde | 0.0288 | TDO2 |  |  |
 Tyrosine biosynthesis IV |  |  | 0.0490 | PCBD1 |
 Vitamin-C transport |  |  | 0.0251 | SLC23A1, GLRX |
 Xenobiotic metabolism signaling | 0.0178 | UGT2B28, HMOX1, ALDH1A2, CES2 |  |  |
Stress response | ||||
 Unfolded protein response | 0.0209 | Hspa1b, HSPA1A/HSPA1B |  |  |
Cancer | ||||
 Molecular mechanisms of cancer |  |  | 0.0013 | SHH, Naip1 (includes others), BMP4, WNT3, BMP2, SMAD7, SMAD6, BMP5, MYC, CCND2, PRKAR2B, ADCY8, FZD2, NOTCH1, PTCH2 |
 Basal cell carcinoma signaling |  |  | 0.0000 | SHH, BMP4, WNT3, GLIS1, BMP2, HHIP, BMP5, FZD2, PTCH2 |
 Bladder cancer signaling |  |  | 0.0155 | MYC, FGF10, FGF14, FGF3, FGF19 |