title: Vitamin D supplementation blocks pulmonary structural and functional changes in a rat model of perinatal vitamin D deficiency.
abstract: Whereas epidemiological data strongly link vitamin D (VD) deficiency to childhood asthma, the underlying molecular mechanisms remain unknown. Although VD is known to stimulate alveolar epithelial-mesenchymal interactions, promoting perinatal lung maturation, whether VD supplementation during this period protects against childhood asthma has not been demonstrated experimentally. Using an in vivo rat model, we determined the effects of perinatal VD deficiency on overall pulmonary function and the tracheal contraction as a functional marker of airway contractility. One month before pregnancy, rat dams were put on either a no cholecalciferol-added or a 250, 500, or 1,000 IU/kg cholecalciferol-added diet, which was continued throughout pregnancy and lactation. At postnatal day 21, offspring plasma 25(OH)D levels and pulmonary function (whole body plethysmography and tracheal contraction response to acetylcholine) were determined. 25(OH)D levels were lowest in the no cholecalciferol-supplemented group, increasing incrementally in response to cholecalciferol supplementation. Compared with the 250 and 500 IU/kg VD-supplemented groups, the no cholecalciferol-supplemented group demonstrated a significant increase in airway resistance following methacholine challenge. However, the cholecalciferol deficiency-mediated increase in tracheal contractility in the cholecalciferol-depleted group was only blocked by supplementation with 500 IU/kg cholecalciferol. Therefore, in addition to altering alveolar epithelial-mesenchymal signaling, perinatal VD deficiency also alters airway contractility, providing novel insights to asthma pathogenesis in perinatally VD-deficient offspring. Perinatal VD supplementation at 500 IU/kg appears to effectively block these effects of perinatal VD deficiency in the rat model used, providing a strong clinical rationale for effective perinatal VD supplementation for preventing childhood asthma.
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, David Geffen School of Medicine, Torrance, California; and.
authors.forename: Methap
authors.initials: M
authors.lastname: Yurt
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, David Geffen School of Medicine, Torrance, California; and.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, David Geffen School of Medicine, Torrance, California; and.
authors.forename: Reiko
authors.initials: R
authors.lastname: Sakurai
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, David Geffen School of Medicine, Torrance, California; and.
authors.forename: Ming
authors.initials: M
authors.lastname: Gong
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, David Geffen School of Medicine, Torrance, California; and.
authors.forename: Sumair M
authors.initials: SM
authors.lastname: Husain
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, David Geffen School of Medicine, Torrance, California; and.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Siddiqui
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, David Geffen School of Medicine, Torrance, California; and.
authors.forename: Maleha
authors.initials: M
authors.lastname: Husain
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, David Geffen School of Medicine, Torrance, California; and.
authors.forename: Patricia
authors.initials: P
authors.lastname: Villarreal
authors.affiliation: Medical Faculty, Department of Biochemistry, Ataturk University, Erzurum, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Akcay
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, David Geffen School of Medicine, Torrance, California; and.
authors.forename: John S
authors.initials: JS
authors.lastname: Torday
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, David Geffen School of Medicine, Torrance, California; and vrehan@labiomed.org.
authors.forename: Virender K
authors.initials: VK
authors.lastname: Rehan
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000517:prevention & control*; D002118:Calcium / Q000097:blood; D002762:Cholecalciferol / Q000008:administration & dosage / Q000627:therapeutic use*; D019587:Dietary Supplements; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D008168:Lung / Q000473:pathology; D016210:Methacholine Chloride / Q000009:adverse effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012129:Respiratory Function Tests; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000188:drug therapy* / Q000517:prevention & control
chemical_list: D016210:Methacholine Chloride; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D; D000469:Alkaline Phosphatase; D002118:Calcium
keywords: Wnt signaling; childhood asthma; epithelial-mesenchymal interactions; lipofibroblast; peroxisome proliferator-activated receptor-γ