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Heydarian, M. ; Oak, P. ; Koschlig, M. ; Kamgari, N. ; Hagemann, M. ; Wjst, M.* ; Hilgendorff, A.

Prenatal vitamin D supplementation mitigates inflammation-related alveolar remodeling in neonatal mice.

Am. J. Physiol. Lung Cell Mol. Physiol. 325, L95-L103 (2023)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
The development of chronic lung disease in the neonate, also known as bronchopulmonary dysplasia (BPD), is the most common long-term complication in prematurely born infants. In BPD, the disease-characteristic inflammatory response culminates in nonreversible remodeling of the developing gas exchange area, provoked by the impact of postnatal treatments such as mechanical ventilation (MV) and oxygen treatment. To evaluate the potential of prenatal treatment regimens to modulate this inflammatory response and thereby impact the vulnerability of the lung toward postnatal injury, we designed a multilayered preclinical mouse model. After administration of either prenatal vitamin D-enriched (VitD+; 1,500 IU/g food) or -deprived (VitD-; <10 IU/kg) food during gestation in C57B6 mice (the onset of mating until birth), neonatal mice were exposed to hyperoxia (FiO2 = 0.4) with or without MV for 8 h at days 5-7 of life, whereas controls spontaneously breathed room air. Prenatal vitamin D supplementation resulted in a decreased number of monocytes/macrophages in the neonatal lung undergoing postnatal injury together with reduced TGF-β pathway activation. In consequence, neonatal mice that received a VitD+ diet during gestation demonstrated less extracellular matrix (ECM) remodeling upon lung injury, reflected by the reduction of pulmonary α-smooth muscle actin-positive fibroblasts, decreased collagen and elastin deposition, and lower amounts of interstitial tissue in the lung periphery. In conclusion, our findings support strategies that attempt to prevent vitamin D insufficiency during pregnancy as they could impact lung health in the offspring by mitigating inflammatory changes in neonatal lung injury and ameliorating subsequent remodeling of the developing gas exchange area.NEW & NOTEWORTHY Vitamin D-enriched diet during gestation resulted in reduced lung inflammation and matrix remodeling in neonatal mice exposed to clinically relevant, postnatal injury. The results underscore the need to monitor the subclinical effects of vitamin D insufficiency that impact health in the offspring when other risk factors come into play.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Bronchopulmonary Dysplasia ; Mechanical Ventilation ; Oxygen Toxicity ; Prenatal Treatment ; Vitamin D; D Deficiency; Mechanical Ventilation; Bronchopulmonary Dysplasia; Lung-disease; Preterm; Growth; Increases; Septation; Apoptosis
ISSN (print) / ISBN 1040-0605
e-ISSN 1522-1504
Zeitschrift American Journal of Physiology - Lung Cellular and Molecular Physiology
Quellenangaben Band: 325, Heft: 2, Seiten: L95-L103 Artikelnummer: , Supplement: ,
Verlag American Physiological Society
Verlagsort Bethesda, Md. [u.a.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Lung Health and Immunity (LHI)
CF Laboratory Animal Services (CF-LAS)
Förderungen Stiftung AtemWeg (LSS AIRR)
Research Training Group Targets in Toxicology of the German Science and Research Organization (DFG)
German Center for Lung Research (DZL, German Ministry of Education and Health(BMBF))
~Helmholtz Zentrum Munchen, Germany
Helmholtz Foundation