Vitamin A Deficiency and the Lung

Abstract

Vitamin A (all-trans-retinol) is a fat-soluble micronutrient which together with its natural derivatives and synthetic analogues constitutes the group of retinoids. They are involved in a wide range of physiological processes such as embryonic development, vision, immunity and cellular differentiation and proliferation. Retinoic acid (RA) is the main active form of vitamin A and multiple genes respond to RA signalling through transcriptional and non-transcriptional mechanisms. Vitamin A deficiency (VAD) is a remarkable public health problem. An adequate vitamin A intake is required in early lung development, alveolar formation, tissue maintenance and regeneration. In fact, chronic VAD has been associated with histopathological changes in the pulmonary epithelial lining that disrupt the normal lung physiology predisposing to severe tissue dysfunction and respiratory diseases. In addition, there are important alterations of the structure and composition of extracellular matrix with thickening of the alveolar basement membrane and ectopic deposition of collagen I. In this review, we show our recent findings on the modification of cell-junction proteins in VAD lungs, summarize up-to-date information related to the effects of chronic VAD in the impairment of lung physiology and pulmonary disease which represent a major global health problem and provide an overview of possible pathways involved.

Retinoic Acid: A Key Regulator of Lung Development

“…Such defects include lung hypoplasia, pulmonary agenesis, lack of esophageal-tracheal septum, and congenital diaphragmatic hernia (CDH) both in animal models and in humans [4,55,142,143]. Dietary vitamin A deficiency (VAD) during pregnancy represents a major concern in developing countries who do not have access to well-balanced food intake and, consequently, are more prone to develop RA-associated fetal lung diseases [3]. The genetic burden, particularly the presence of mutations in the RA machinery, also contributes to developing more or less dramatic lung phenotypes.…”

“…Chronic respiratory disorders such as pulmonary fibrosis, lung cancer, emphysema, and COPD, are also VAD-related. Likewise, under VAD conditions, childhood asthma and respiratory infections are promoted [3,145]. On the other hand, retinoids can be applied to promote alveolarization of premature infants at risk of bronchopulmonary dysplasia; or to stimulate the alveolar development and de novo surfactant production of CDH-associated pulmonary hypoplasia [146][147][148].…”

“…In the adult, RA is crucial for immune, nervous and reproductive systems, as well as for vision and skin renewal. Throughout embryogenesis, RA acts as a potent morphogen that mediates cellular signaling and transcriptional regulation, thus modulating numerous aspects of embryo development [1][2][3]. RA levels must be tightly regulated, if not, RA can act as a teratogen, rather than a morphogen.…”

Role of vitamin A in health and illness

“…Changes involve keratinizing metaplasia, necrosis of mucosa, and focal loss of ciliated cells. A new-born has impaired lung function, decreased number of alveoli, defective protection against infections, and are at higher risk for the development of acute diseases in childhood and chronic diseases in adulthood, including lung cancer [61,62].…”

“…Endemic vitamin A deficiency is related to keratinization of the bronchi and tracheae, observed to occur even before alterations in the eye. Another effect of vitamin A deficiency is low FVC (forced vital capacity), a marker of airway obstruction and other extracellular matrix alterations, mostly in kidney, lung and liver [61,63].…”