Table III.
Signal pathways associated with TSP-2 in CVDs.
| Domains | Interacting molecules | Associated signal pathways | Effect | (Refs.) | Inhibitors | (Refs.) |
|---|---|---|---|---|---|---|
| N-terminal domain | LRP | Phagosome | Internalization and degradation of TSP-2 | (160,161) | Heparin | (157) |
| Participates in cell signaling with cell surface calreticulin | (10,13,14) | |||||
| Calreticulin | Focal adhesion | Induces focal adhesion disassembly and cell migration | 10,13,14) | |||
| Integrin α4β1 | ECM-receptor interaction | Mediates adhesion of T cells | (134) | |||
| Integrin α6β1 | ECM-receptor interaction | Mediates adhesion of microvascular endothelium to immobilized TSP-2 | (19) | |||
| Versican | ECM-receptor interaction | Inhibits VSMC inflammatory response (significantly weaker compared with TSP-1) | (11) | Heparin | (11) | |
| Type I repeats domain | MMP2 | ECM homeostasis | Inhibition of MMP2 activity | (20) | - | - |
| Mediation of collagen fibrillogenesis | (113) | - | - | |||
| Clearance of extracellular MMP2 by fibroblasts | (157) | - | - | |||
| MMP9 | ECM homeostasis | Regulate collagen homeostasis | (20) | - | - | |
| PI3K-AKT pathway | Inhibit cell invasion | (158) | - | - | ||
| CD36 | PI3K-AKT pathway | Anti-angiogenic activity | (25,26) | - | - | |
| β1 integrin | ECM-receptor interaction | Promotes adhesion of the cells that express β1 integrin | (28) | β1 blocking antibody, disintegrins | (28) | |
| Type II repeats domain | β1 integrin | ECM-receptor interaction | Promotes adhesion of the cells that express β1 integrin | (28) | β1 blocking antibody, disintegrins | (28) |
| EGFR | PI3K-AKT pathway | Increases cell migration | (140) | - | - | |
| Type III repeats domain | Calcium | Calcium pathway | Inhibits vascular diseases | (38) | - | - |
| Maintains the homeostasis between the vasodilation and the vasoconstriction | (163) | - | - | |||
| Integrin αIIβ3 | ECM-receptor interaction | Promotes TSP-1 binding with platelets | (136) | - | - | |
| Integrin αvβ3 | ECM-receptor interaction | Promotes TSP-1 binding with platelets | (136) | - | - | |
| FGF2 | PI3K-AKT pathway | Antiangiogenic activity | (43) | Calcium and heparin | (36) | |
| C-terminal domain | Calcium | Calcium pathway | Inhibits vascular diseases | (38) | - | - |
| Maintains the homeostasis between vasodilation and vasoconstriction | (163) | - | - | |||
| CD47 | ECM-receptor interaction | Promotes the cell adhesion to immobilized TSP-2 | (18) | - | - | |
| Unknown | CYP1B1 | PI3K-AKT pathway | Promotes a pro-angiogenic phenotype via the regulation of the oxidative stress | (165) | - | - |
| NO | PI3K-AKT pathway | Negatively regulates TSP-2 transcription and induces angiogenesis | (166) | - | - | |
| ADAMTS1 | ADAMTS1-TSP2 pathway | Promotes wound closure and inhibits angiogenesis | (167) | - | - |
LRP, lipoprotein receptor-related protein; MMP, matrix metalloprotein; EGFR, epidermal growth factor receptor; FGF2, fibroblast growth factor 2; CYP1B1, cytochrome p450 1b1; NO, nitric oxide; ADAMTS, disintegrin and metalloproteinase with thrombospondin motifs; TSP-2, thrombospondin-2; ECM, extracellular matrix; VSMC, vascular smooth muscle cells; LRP, low-density lipoprotein receptor related protein.