Table 5.
Ingenuity Pathway Analysis of ReninAAV db/db uNx and eNOS−/−db/db models
| Pathways Changed | ReninAAV −log(P Value) | eNOS−/− db/db −log(P Value) |
|---|---|---|
| Pathways shared in ReninAAV db/db uNx and eNOS−/− db/db models | ||
| Hepatic fibrosis/hepatic stellate cell activation | 11.6 | 9 |
| Acute-phase response signaling | 10.1 | 8.46 |
| Granulocyte adhesion and diapedesis | 9.23 | 12.3 |
| Dendritic cell maturation | 8.32 | 10.4 |
| Role of macrophages, fibroblasts, and endothelial cells in rheumatoid arthritis | 7.51 | 2.86 |
| Atherosclerosis signaling | 7.39 | 8.2 |
| Antigen presentation pathway | 7.22 | 6.66 |
| Role of NFAT in regulation of the immune response | 7.13 | 2.34 |
| Agranulocyte adhesion and diapedesis | 7.01 | 8.75 |
| TREM1 signaling | 6.83 | 3.26 |
| Pathways unique to ReninAAV db/db uNx model | ||
| Valine degradation I | 7.54 | 0.31 |
| Tryptophan degradation III (eukaryotic) | 5.01 | 0.29 |
| Isoleucine degradation I | 4.95 | 0.39 |
| PI3K signaling in B lymphocytes | 4.83 | 1.03 |
| Ethanol degradation II | 3.96 | 1.04 |
| Leucine degradation I | 3.95 | 1.38 |
| LPS/IL-1–mediated inhibition of RXR functiona | 3.66 | 0.98 |
| Oxidative ethanol degradation III | 3.6 | 1.57 |
| Ketogenesis | 3.49 | 0.50 |
| Noradrenaline and adrenaline degradation | 3.4 | 0.94 |
| PPARα/RXRα activation | 3.35 | 1.35 |
| Apoptosis signaling | 3.35 | 0.66 |
| Macropinocytosis signaling | 3.32 | 1.57 |
| Ketolysis | 3.29 | 0.58 |
| PPAR signaling | 3.17 | 1.33 |
| STAT3 pathway | 3.1 | 1.74 |
| TWEAK signaling | 3.08 | 1.45 |
| Fcγ receptor–mediated phagocytosis in macrophages and monocytesa | 3.08 | 1.31 |
| Aryl hydrocarbon receptor signalinga | 3.04 | 1.28 |
| Axonal guidance signalinga | 2.94 | 0.38 |
Top pathways shared between the ReninAAV db/db uNx model and the eNOS−/−db/db model and the top 20 pathways unique to the ReninAAV db/db uNx model were identified. Pathways were identified by those with statistical significance (−log[P value]) in both models for shared genes and models for unique genes that were only statistically significant for the ReninAAV db/db uNx model but did not reach statistical significance in the eNOS−/−db/db model.
a
Pathways unique to the ReninAAV db/db uNx model that were additionally found to be dysregulated in human DKD datasets.