ABSTRACT
A number of respiratory defects were described in early vitamin A deciency syndrome embryos, but were characterized as rare anomalies [1]. It is known today that vitamin A acquired from dietary retinol or carotenoids undergoes oxidative conversion to all-trans or 9-cis retinoic acid (RA), before exerting its biological effects during embryogenesis and after birth in lung tissue [2]. The RA isomers exert their biological effects by binding to RA receptors and retinoid-X receptors, respectively [3]. The two receptors belong to the steroid hormone receptor superfamily. They are able to form heterodimers, which bind to RA-responsive elements in genes expressed in the epithelium of pulmonary tissue. Rat embryos develop lung hypoplasia when RA in the maternal diet is reduced [4]. Retinoid acid receptors (RARs) are expressed throughout lung development, and in a mouse model (RAR compound null mutant mice), it could be shown that those animals develop left lung agenesis and also lung hypoplasia [5]. In addition, a wide spectrum of RA synthesizing, metabolizing, and binding proteins are found in developing lung tissue [6-8]. It is interesting that besides the liver, the lung is also a large store of retinoids in the body. The retinoids are stored as retinyl esters in lipid-laden broblasts that are abundant in the alveolar wall and often in close vicinity to type II pneumocytes [9-11]. Action of RA in lung development is well regulated. For initial budding, RA signaling is required. Thereafter, RA levels are down-regulated by RA-degrading enzymes to enable more distal branching and distal airway formation [8,12 ]. Furthermore, it could be shown that RARs are also required for correct lung alveolar septation [13-15]. A role for
Introduction ............................................................................................................ 273 Bronchopulmonary Dysplasia ................................................................................ 274 Asthma ................................................................................................................... 276 Chronic Obstructive Pulmonary Disease/Emphysema .......................................... 278 Cystic Fibrosis Lung Disease ................................................................................. 279 Conclusions ............................................................................................................ 282 References .............................................................................................................. 283
RA in alveoli formation is supported by the nding that exogenous RA can stimulate alveoli formation in immature rat and mouse lung [10,16,17].
