16THE IMPORTANCE OF VITAMIN AThe Importance of Vitamin Afor the Development<strong>and</strong> Function of Lungs inNewbornsHans Konrad BiesalskiUniversity of Hohenheim,Stuttgart, GermanySummaryVitamin A is essential for growth <strong>and</strong> development, inparticular for the adequate maturation of the lung in lateembryogenesis. If the developing embryo is not supplied withsufficient amounts of vitamin A delivered from the mother, embryoniclung retinyl ester stores remain low. As a consequence,the sources for retinol <strong>and</strong> subsequently the active metaboliteretinoic acid, important for gene expression in the lung, are notsufficiently available during the time of lung maturation.Low vitamin A stores in the lung impair the expression of surfactantproteins, alveoli formation <strong>and</strong> the development of therespiratory epithelium. Newborns with low vitamin A storesare at risk for respiratory diseases such as bronchopulmonarydysplasia <strong>and</strong> frequent infections in early childhood.IntroductionVitamin A is essential for the growth <strong>and</strong> development of cells<strong>and</strong> tissues. In its active form, retinoic acid (RA), it controls regulardifferentiation as a lig<strong>and</strong> for retinoic acid receptors (RAR,RXR). 1,2 Vitamin A plays a substantial role in the respiratoryepithelium <strong>and</strong> the lung. In the presence of moderate vitamin Adeficiency the incidence of diseases of the respiratory tract isconsiderably increased. Repeated respiratory infections can beinfluenced therapeutically by moderate vitamin A supplementation.3,4,5 Besides its importance for lung function, vitamin A isalso responsible for the development of many tissues <strong>and</strong> cells,as well as for embryonic lung development. Recent studies havedemonstrated that this occurs by various expressions of retinoidreceptors, as well as by time-dependent changes of the vitaminA concentration in the tissue. Where maternal vitamin A isdeficient fetal lung maturation might be seriously impaired, withconsequences for postnatal function.The influence of vitamin A on the maturation<strong>and</strong> differentiation of the lungVitamin A <strong>and</strong> its major active metabolite RA have a profoundinfluence on the alveolar development, maintenance <strong>and</strong> functionof the lung. Type II alveolar cells synthesize <strong>and</strong> secretesurfactant. 6 RA is able to stop – dependent on its concentration7 – the expression of the surfactant-protein A (SP-A) in humanfetal lung explants. Insulin, TGF- <strong>and</strong> high concentrationsof glucocorticoids can also down-regulate the expression of SP-A-mRNA, 8 but lower concentrations of glucocorticoids stimulatethe expression of these genes. 9 In contrast, the expression ofSP-A-mRNA is increased by hyperoxia in rats 10 <strong>and</strong> by dexamethasonein human fetal lung explants. 7Type PGE₂ prostagl<strong>and</strong>ins are able to increase surfactantsynthesis. Under the influence of EGF (epidermal growth factor)the formation of prostagl<strong>and</strong>in rises, especially that of PGE₂. Onthe other h<strong>and</strong>, the expression of the EGF receptor is increasedby RA. EGF increases proliferation of the lung tissues, leadingto an amplified formation of surfactant phospholipids. 11 RA <strong>and</strong>EGF both lead to an increase (40%, 80%) in the secretion ofPGE₂ in fetal lung cells of the rat in vitro. 12 The combination ofRA <strong>and</strong> EGF, however, leads to a more than a six-fold increasein the secretion of PGE₂. Consequently, RA can interfere in lungdevelopment due to its modulating effect on the expression ofEGF <strong>and</strong> the subsequent PGE₂-induced surfactant formation.Sufficient <strong>and</strong> continuous availability of vitamin A (either on theblood pathway or from local storage sites) is pivotal, especially
SIGHT AND LIFE | VOL. 25 (1) | <strong>2011</strong>17“Repeated respiratoryinfections can be infl uencedtherapeutically by moderatevitamin A supplementation.”
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