Table 2.
Notable Sources and Sites of Action of GDF-15
| Confirmed Sources of High-Level GDF-15 Production | Comments | References |
|---|---|---|
| Macrophages | Induced by LPS or proinflammatory cytokines | (9) |
| Erythroblasts | (95) | |
| Placenta | Crucial to maintaining pregnancy; low levels predict fetal wastage | (11, 24, 25) |
| Prostate gland | Expressed by benign and especially malignant epithelium; positively regulated by androgens | (6, 96) |
| Airway epithelial cells | Induced by cigarette smoke; upregulates MUC5AC and induces apoptosis | (76, 77) |
| Vascular endothelial cells (including pulmonary microvascular and HUVEC) | Supports survival in response to hypoxia via activation and nuclear translocation of HIF-1α | (65, 66) |
| Cardiac myocytes | Produced in congenital heart disease, myocardial infarction, ischemia–reperfusion | (45, 97) |
| White fat | Secreted by adipocytes |
| Sites of GDF-15 Action | Comments | References |
|---|---|---|
| Brain | Binds to GFRAL in area postrema and nucleus of the tractus solitarius and suppresses appetite; circulates in cerebrospinal fluid; has potent neuroprotective effects | (21, 38–41, 90, 91) |
| Neutrophils | Blocks integrin-mediated arrest | (32, 34) |
| Platelets | Inhibits integrin-mediated aggregation | (33) |
| Liver | Inhibits secretion of hepcidin; inhibits production of growth hormone, inducing growth retardation in children with congenital heart disease | (35, 36, 97) |
| Kidney | Mediates ductal lengthening and induces proliferation of acid-secreting intercalated cells during adaptation to metabolic acidosis | (98) |
Definition of abbreviations: GDF-15 = growth differentiation factor 15; GFRAL = glial cell line–derived neurotrophic factor family receptor-α–like; HIF-1α = hypoxia-inducible factor 1α; HUVEC = human umbilical vein endothelial cells.