Table I.
Biological functions of GDF15.
| Actions | Experimental models | Mechanisms | (Refs.) |
|---|---|---|---|
| Angiogenesis | |||
| Pro-angiogenesis | Endothelial colony forming cells generated from adult human blood | ↑NO, ↑AKT, ERK1/2 and SMAD2 | (57) |
| HUVEC | ↑Cyclin D1 and E, ↑retinoblastoma phosphorylation and E2F-1 nuclear translocation | (58) | |
| HUVEC | ↓p53, hypoxia-induced factor-1α | (59) | |
| Hepatocellular carcinoma | ↑Src and AKT, MAPK and NF-κB downstream | (62) | |
| Anti-angiogenesis | HUVEC | ↓Connective tissue growth factor 2/focal adhesion kinase | (63) |
| Apoptosis | |||
| Pro-apoptosis | Prostate cancer cells | ↑Methylseleninic acid, ↑caspase-dependent apoptosis | (66,67) |
| Activated macrophages | ↑ PARP, caspase-3 or AIF | (68) | |
| A459 cells | ↑caspase-9 and caspase-3; ↓ERK1/2 and p38 MAPK phosphorylation | (69) | |
| Anti-apoptosis | HUVEC | ↑PI3K/AKT/ endothelial nitric oxide synthase; ↓NF-κB/JNK | (70) |
| Patients with pulmonary hypertension | ↑AKT | (71) | |
| Lipid metabolism | Transgenic GDF15 mice | ↑Key thermogenic and lipolytic genes | (73) |
| Mice fed with high-fat diet | ↑Glial cell-derived neurotrophic factor receptor α-like | (74) | |
| Patients with non-alcoholic steatohepatitis | ↑β-arrestin1; ↑β-oxidation genes; ↓fatty acids | (75) | |
| Fasted mice | ↑Fatty acid β-oxidation and ketogeneis | (76) | |
| Inflammation | |||
| Anti-inflammation | Mice treated with lipopolysaccharide | ↓Monocyte chemoattractant protein-1, TNF-α, transforming growth factor-β-activated kinase 1 phosphorylation and NF-κB | (79,81) |
| Mice | ↑Triglyceride metabolism | (77) | |
| Pro-inflammation | Human GDF15 transgenic mice | ↓IFN-λ2/3 mRNA | (78) |
| Human transgenic mice tracheal epithelial cells | ↓IFN-λ1/IL-29 | (78) |
↑, enhancement or promotion; ↓, reduction or inhibition; GDF-15, growth differentiation factor-15; HUVECs, human umbilical cord vascular endothelial cells; IFN, interferon.