title: Retinoic acid rescues alveolar hypoplasia in the calorie-restricted developing rat lung.
abstract: Infants born with intrauterine growth retardation (IUGR) are at increased risk of adverse pulmonary outcomes at birth, including meconium aspiration and persistent pulmonary hypertension. Preterm infants with IUGR are at especially high risk of developing bronchopulmonary dysplasia (BPD), a disease hallmarked by alveolar hypoplasia. Although vitamin A supplementation has been shown to decrease the incidence of BPD or death in preterm very low birth weight infants, its potential to reduce BPD or death in preterm infants with IUGR remains unknown. We used a well-characterized rat model of caloric restriction to mimic IUGR and determine the impact of IUGR on lung development. We hypothesized that retinoic acid treatment would preserve alveolar formation through increases in key signaling molecules of the retinoic acid signaling pathway. Our results showed that alveolar hypoplasia caused by caloric restriction can be reversed with refeeding, and that retinoic acid prevents the alveolar hypoplasia coincident with the increased expression of elastin and retinoic acid receptor-α and decreased transforming growth factor-β activity in developing rat lungs. These findings suggest that alveolar hypoplasia attributable to caloric restriction is reversible, and raises the possibility that retinoic acid therapy may prove a useful strategy to prevent adverse pulmonary sequelae such as BPD in preterm infants with IUGR.
authors.affiliation: Neonatal Research Center, Division of Neonatology and Developmental Biology, Department of Pediatrics, David Geffen School of Medicine, University of California at Los Angeles, 10833 Le Conte Ave., Mailcode 175217, B2-375 MDCC, Los Angeles, CA 90095-1752, USA. vlondhe@mednet.ucla.edu
authors.forename: Vedang A
authors.initials: VA
authors.lastname: Londhe
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Maisonet
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lopez
authors.forename: Bo-Chul
authors.initials: BC
authors.lastname: Shin
authors.forename: Jasmine
authors.initials: J
authors.lastname: Huynh
authors.forename: Sherin U
authors.initials: SU
authors.lastname: Devaskar
mesh_terms: D000818:Animals; D031204:Caloric Restriction; D004549:Elastin / Q000378:metabolism; D005260:Female; D006965:Hyperplasia / Q000517:prevention & control*; D008168:Lung / Q000196:embryology*; D018811:Maternal Exposure; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: C000607073:Rara protein, rat; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D016212:Transforming Growth Factor beta; C082927:retinoic acid binding protein I, cellular; D014212:Tretinoin; D004549:Elastin