Table 2.
Top 20 canonical IPA pathways differentially regulated in cord blood monocytes from preterm and term infants.
| Ingenuity canonical pathways | Signaling pathway categories (IPA) |
–log (p-value) |
Relation to inflammation and/or monocyte function (select references) |
|---|---|---|---|
| Regulation of Actin-based Motility by Rho | Neurotransmitters and Other Nervous System Signaling | 5.72 | Rho is a family of GTPases, important in innate and adaptive immunity (35) |
| Thrombin Signaling | Cardiovascular Signaling | 5.54 | Involved in monocyte regulation of systemic coagulation in (36) |
| RhoGDI Signaling | Intracellular and Second Messenger Signaling | 4.98 | Involved in Rho-regulation; important for innate and adaptive immunity (35, 37) |
| Integrin Signaling | Cell Cycle Regulation; Cellular Growth, Proliferation and Development; Intracellular and Second Messenger Signaling | 4.75 | Critical in monocyte trafficking and vessel wall adhesion (38) |
| Actin Cytoskeleton Signaling | Cell Cycle Regulation; Cellular Growth, Proliferation and Development; Intracellular and Second Messenger Signaling | 4.63 | Regulates locomotion, phagocytosis, and cell shape in leukocytes including monocytes (39) |
| Relaxin Signaling | Growth Factor Signaling; Organismal Growth and Development | 4.5 | An insulin-like peptide with properties important for recruitment of peripheral blood mononuclear cells to sites of inflammation (40) |
| Cellular Effects of Sildenafil (Viagra) | Cardiovascular Signaling; Disease-Specific Pathways | 4.34 | N/A |
| Ephrin B Signaling | Neurotransmitters and Other Nervous System Signaling; Organismal Growth and Development | 4.15 | Ephrin proteins are involved in inflammation in vascular endothelium (41) including in monocytes (42) |
| Signaling by Rho Family GTPases | Intracellular and Second Messenger Signaling | 4.11 | Rho is a family of GTPases, important in innate and adaptive immunity (35) |
| Molecular Mechanisms of Cancer | Cancer; Disease-Specific Pathways | 4.1 | N/A |
| Cardiac β-adrenergic Signaling | Cardiovascular Signaling | 4.07 | N/A |
| Protein Kinase A Signaling | Intracellular and Second Messenger Signaling | 4 | N/A |
| Synaptogenesis Signaling Pathway | Neurotransmitters and Other Nervous System Signaling; Organismal Growth and Development | 3.91 | N/A |
| Leukocyte Extravasation Signaling | Cellular Immune Response | 3.9 | Monocytes immune surveillance and trafficking across vasculature (42) |
| Germ Cell-Sertoli Cell Junction Signaling | Cellular Growth, Proliferation and Development | 3.89 | N/A |
| IL-8 Signaling | Cellular Immune Response; Cytokine Signaling | 3.88 | Commonly found in early-onset neonatal sepsis (43) |
| Breast Cancer Regulation by Stathmin1 | Cancer; Disease-Specific Pathways | 3.86 | N/A |
| Epithelial Adherens Junction Signaling | Cellular Growth, Proliferation and Development | 3.73 | N/A |
| Androgen Signaling | Nuclear Receptor Signaling | 3.52 | N/A |
| CXCR4 Signaling | Cellular Immune Response; Cytokine Signaling | 3.4 | Involved in maturation and replenishment of monocytes (44) |
Analysis is based on 500 genes differentially expressed between term and preterm groups and analyzed by Ingenuity Pathway Analysis (IPA) (Qiagen Bioinformatics).