Table 2 Canonical pathways and supporting differentially expressed genes (DEGs) that were commonly regulated by 0.25, 0.5 and 1.0Â mg/L nominal concentrations of depleted uranium (DU)
Apical toxicological category | Ingenuity canonical pathways | Supporting DEGs |
|---|---|---|
Amino acids degradation | Tryptophan Degradation to 2-amino-3-carboxymuconate Semialdehyde | KMO↑,TDO2↑ |
Valine Degradation I | DLD↑,ALDH6A1↑,BCKDHB↑ | |
Cell growth and development | Epithelial Adherens Junction Signaling | MET↑,CDH1↓,MYL6↑,ARPC5L↑,MYH7↑,TCF7L1↓,CDC42↑,ACTG1↓,TUBA1B↑ |
Sertoli Cell-Sertoli Cell Junction Signaling | MAP2K4↑,CDH1↓,MAPK14↓,PPAP2B↑,CLDN18↓,IGSF5↑,CDC42↑,ACTG1↓,TUBA1B↑ | |
Germ Cell-Sertoli Cell Junction Signaling | MAP2K4↑,CDH1↓,MAPK14↓,RHOB↑,PPAP2B↑,CDC42↑,RHOF↑,ACTG1↓,TUBA1B↑,FNBP1↑ | |
Remodeling of Epithelial Adherens Junctions | MET↑,DNM1↓,CDH1↓,ARPC5L↑,ACTG1↓,TUBA1B↑ | |
ILK Signaling | MAP2K4↑,CDH1↓,FN1↓,MYL6↑,RHOB↑,PPAP2B↑,MYH7↑,CDC42↑,RHOF↑,ACTG1↓,FNBP1↑,DSP↓ | |
Actin Cytoskeleton Signaling | FN1↓,MYL6↑,ARPC5L↑,PIKFYVE↑,RDX↓,MYH7↑,CDC42↑,GIT1↓,TTN↓,ACTG1↓ | |
Cellular immune response | HMGB1 Signaling | MAP2K4↑,MAPK14↓,RHOB↑,CDC42↑,RHOF↑,FNBP1↑ |
IL-22 Signaling | MAP2K4↑,JAK1↓,MAPK14↓ | |
Free radical scavenging and apoptosis | Mitochondrial Dysfunction | MAP2K4↑,SDHA↑,COX6B1↑,CPT1A↓,UQCR11↑,SDHC↑,COX7A2L↑,DHODH↑,MAOB↓,PRDX3↑,TXN2↑,UQCRFS1↑,NDUFS2↑,SDHD↑,NDUFA3↑,AIFM1↑,COX15↑ |
NAD biosynthesis II (from tryptophan) | KMO↑,TDO2↑,QPRT↑ | |
Tight Junction Signaling | MYL6↑,RAB13↑,CLDN18↓,IGSF5↑,MYH7↑,CDC42↑,ACTG1↓,CSTF3↑ | |
Hematological response | Hypoxia Signaling in the Cardiovascular System | TP53↑,P4HB↑,HSP90AB1↑,SUMO1↑,NQO1↑,UBE2D4↓,UBE2E1↑ |
Inhibition of Angiogenesis by TSP1 | MAP2K4↑,HSPG2↑,TP53↑,MAPK14↓ | |
Intrinsic Prothrombin Activation Pathway | F10↑,F9↑,COL18A1↓ | |
Coagulation System | F10↑,F9↑,F7↑,SERPINF2↑,SERPIND1↑ | |
Role of JAK family kinases in IL-6-type Cytokine Signaling | MAP2K4↑,JAK1↓,MAPK14↓ | |
Intracellular signal transduction | Signaling by Rho Family GTPases | MAP2K4↑,CDH1↓,RHOB↑,MYL6↑,ARPC5L↑,GNB2L1↑,SEPT7↑,RDX↓,PIKFYVE↑,RHOF↑,CDC42↑,ACTG1↓,FNBP1↑ |
Actin Nucleation by ARP-WASP Complex | RHOB↑,ARPC5L↑,CDC42↑,RHOF↑,FNBP1↑ | |
RhoA Signaling | MYL6↑,ARPC5L↑,SEPT7↓,PIKFYVE↑,RDX↓,TTN↓,ACTG1↓ | |
Glucocorticoid Receptor Signaling | MAP2K4↑,GTF2A2↑,POLR2F↑,JAK1↓,MAPK14↓,HSP90AB1↑,SUMO1↑,GTF2E2↑,HLTF↑,POLR2I↑,TAF13↑ | |
RhoGDI Signaling | CDH1↓,MYL6↑,RHOB↑,ARPC5L↑,GNB2L1↑,PIKFYVE↑,RDX↓,CDC42↑,RHOF↑,ACTG1↓,FNBP1↑ |