Table 1.
Variation of the expression and roles of netrins & semaphorins in inflammatory –related pathologies.
Recapitulative listing of studies that describe the impact of modulating levels of netrins and semaphorins in inflammatory diseases.
| Diseases | Neuronal Cue | Function | Reference |
|---|---|---|---|
|
| |||
| Atherosclerosis | ↑ Netrin-1/UNC5b | -Prevented macrophage foam cell emigration out of arterial wall | [52, 54] |
| ↑ Sema3E | -Regulated macrophage polarization and migration | [53, 55] | |
| Netrin-1/Sema3A | -Regulated monocyte adhesion to endothelium | [62] | |
|
| |||
| Obesity | ↑ Netrin-1/UNC5b | -Trapped adipose tissue macrophages in the white adipose tissue | [57] |
| ↑ Sema3E/PlexinD1 | -Reported to have pro-migratory functions in ATM; acts as chemoattractant for immune cells and regulates macrophage migration | [58] | |
|
| |||
| Cardiac Failure | Netrin-1/UNC5b | -Increased inflammatory status and accumulation of neutrophils/macrophages | [56, 59] |
| ↑Sema4D | -Plasma soluble form found in cohort of heart failure patients | [48] | |
|
| |||
| Kidney Injury | ↑ Sema3A ↑ Netrin-1 |
- Decreased injury when genetically deleted; excess disrupts glomerular filtration barrier; increased in urine following liver transplant | [49] |
|
| |||
| Rheumatoid Arthritis | ↑ Sema4A/PlexinB1 | - Promoted migration of synovial fibroblasts; found in serum and synovial fluid | [41] |
| ↑ Sema7a | - Increased Th1/Th17 cytokine secretion & T-bet upregulation in T cells | [42] | |
| ↑ Netrin-1 | -Increased in macrophages in inflamed areas of bone resorption; associated with osteoclast differentiation | [69, 71] | |