Inhaled Vitamin D: A Novel Strategy to Enhance Neonatal Lung Maturation.
The physiologic vitamin D (VD), 1α,25(OH)2D3(1,25D) is a local paracrine/autocrine effecter of fetal lung maturation. By stimulating alveolar type II cell and lipofibroblast proliferation and differentiation, parenterally administered 1,25D has been shown to enhance neonatal lung maturation; but due to the potential systemic side effects of the parenteral route, the translational value of these findings might be limited. To minimize the possibility of systemic toxicity, we examined the effects of VD on neonatal lung maturation, when delivered directly to lungs via nebulization.



One-day-old rat pups were administered three different doses of 1,25D and its physiologic precursor 25(OH)D (25D), or the diluent, via nebulization daily for 14 days. Pups were sacrificed for lung, kidneys, and blood collection to determine markers of lung maturation, and serum 25D and calcium levels.



Compared to controls, nebulized 25D and 1,25D enhanced lung maturation as evidenced by the increased expression of markers of alveolar epithelial (SP-B, leptin receptor), mesenchymal (PPARγ, C/EBPα), and endothelial (VEGF, FLK-1) differentiation, surfactant phospholipid synthesis, and lung morphology without any significant increases in serum 25D and calcium levels.



Inhaled VD is a potentially safe and effective novel strategy to enhance neonatal lung maturation.
Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, David Geffen School of Medicine at UCLA, 1124 West Carson Street, Torrance, CA, 90502, USA.
Sneha K
SK
Taylor
Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, David Geffen School of Medicine at UCLA, 1124 West Carson Street, Torrance, CA, 90502, USA.
Reiko
R
Sakurai
Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, David Geffen School of Medicine at UCLA, 1124 West Carson Street, Torrance, CA, 90502, USA.
Tokusho
T
Sakurai
Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, David Geffen School of Medicine at UCLA, 1124 West Carson Street, Torrance, CA, 90502, USA. vrehan@labiomed.org.
Virender K
VK
Rehan
D000280:Administration, Inhalation; D056809:Alveolar Epithelial Cells / Q000502:physiology; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002117:Calcitriol / Q000008:administration & dosage* / Q000009:adverse effects; D002118:Calcium / Q000097:blood; D002454:Cell Differentiation / Q000187:drug effects; D002794:Choline / Q000378:metabolism; D004727:Endothelium / Q000502:physiology; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D008648:Mesoderm / Q000502:physiology; D047495:PPAR gamma / Q000378:metabolism; D037701:Pulmonary Surfactant-Associated Protein B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism; D014304:Triolein / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014807:Vitamin D / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D014815:Vitamins / Q000008:administration & dosage* / Q000009:adverse effects
D022763:CCAAT-Enhancer-Binding Protein-alpha; D047495:PPAR gamma; C000613696:PPAR gamma, rat; D037701:Pulmonary Surfactant-Associated Protein B; D018167:Receptors, Calcitriol; D054411:Receptors, Leptin; D042461:Vascular Endothelial Growth Factor A; D014815:Vitamins; C467498:vascular endothelial growth factor A, rat; D014304:Triolein; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D040301:Vascular Endothelial Growth Factor Receptor-2; D002117:Calcitriol; D002794:Choline; D002118:Calcium
Active vitamin D; Bronchopulmonary dysplasia; Childhood asthma; Lung development; Prematurity