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Vitamin D and Lung Development in Early Life

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Vitamin D and the Lung

Part of the book series: Respiratory Medicine ((RM,volume 3))

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Abstract

Lung morphogenesis is characterized by a complex sequence of cell–cell interactions culminating in the mature airways and alveolar structure of the lung orchestrated by a complex array of spatiotemporally specific transcription factors, growth factors, and physical forces. Parathyroid hormone-related protein (PTHrP) produced by the alveolar epithelium induces adepithelial fibroblast differentiation by stimulating peroxisome proliferator-activated receptor gamma (PPARγ), which inhibits Wnt stimulation of smooth muscle actin, the cellular hallmark of asthma, causing lipofibroblast differentiation. The mature lipofibroblast produces leptin, stimulating epithelial type II cell differentiation, culminating in alveolar homeostasis. These underlying cell–molecular mechanisms provide a functional genomic model for lung development and homeostasis, and how they can be affected by vitamin D obtained both from the diet and by the action of ultraviolet B light on 7-dehydrocholesterol. We review human and animal data showing how vitamin D plays a role in lung cell–molecular development and how its deficiency may alter lung structural and functional development, leading to an asthma phenotype. Even deeper insights to the etiology of asthma come from the evolutionary overlap between PTHrP/PPARγ, Wnt signaling, and environmental factors, offering a mechanistic framework for considering the roles of a variety of vitamin D-related effects on platelet-derived growth factor, late gestation lung 1, vitamin D-upregulated protein, and transforming growth factor-beta 1. Such molecular data for vitamin D deficiency affecting lung development experimentally, combined with evidence for an association between vitamin D deficiency and asthma in preterm infants, are considered in light of the currently recommended but untested daily required doses for vitamin D in term and preterm healthy and sick infants.

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Acknowledgments

Grant support: NIH (HL075405, HL55268, HD51857, HD058948, and HL107118) and the TRDRP (14RT-0073, 15IT-0250, 17RT-0170).

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  1. 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

    Virender K. Rehan & John S. Torday

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Correspondence to Virender K. Rehan .

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  1. Channing Laboratory, Division of Pulmonary and Critical Care, Harvard Medical School, Brigham and Wome, 181 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Augusto A. Litonjua

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Rehan, V.K., Torday, J.S. (2012). Vitamin D and Lung Development in Early Life. In: Litonjua, A. (eds) Vitamin D and the Lung. Respiratory Medicine, vol 3. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-888-7_3

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