Pregnancy and neonatal period/Bronchopulmonary dysplasia (BPD) |
Promotes proliferation and differentiation in fetal lung development |
(19) |
|
Maternal serum levels increase throughout during pregnancy |
(12) |
|
High serum levels in term neonates that decline postnatally |
(20) |
|
Upregulated in neonatal mice exposed to hyperoxia in vivo
|
(21) |
|
Upregulated in pulmonary epithelial and endothelial cells exposed to hyperoxia |
(22) |
|
GDF15 loss leads to decreased cell viability and increased oxidative stress |
(23) |
Chronic Obstructive Pulmonary Disease (COPD) |
Higher serum levels are associated with increased morbidity and mortality |
(4, 24) |
|
Mediates smoking-induced inflammation and cellular senescence |
(25–27) |
|
Promotes mucin production in ciliated epithelial cells |
(28) |
|
Exacerbates lung inflammation secondary to infection |
(29) |
|
Contributes to cachexia: GFRAL mediated signaling, induces lipolysis and promotes muscle wasting |
(30–33) |
Pulmonary Hypertension (PH) |
Associated with prognosis and response to therapy |
(34–36) |
|
Levels increased in pediatric PH related to congenital heart disease |
(37) |
|
Associated with increase in right atrial and pulmonary capillary wedge pressure |
(34) |
|
Induces muscle atrophy that is reversed by TAK1 inhibitor |
(38) |
|
Promotes angiogenesis and hinders endothelial cell apoptosis |
(39, 40) |
Lung Fibrosis |
Associated with disease severity |
(41) |
|
Associated with higher odds of interstitial lung abnormality |
(42) |
|
Activates fibroblasts and M2 macrophages |
(40) |
|
Prevents the activation of fibroblasts during lung remodeling |
(43) |