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Retinoic acid rescues alveolar hypoplasia in the calorie-restricted developing rat lung
Vedang A Londhe1, Tiffany M Maisonet, Benjamin Lopez
1Neonatal 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
Insights
Intrauterine growth retardation (IUGR) in preterm infants increases the risk of lung disease. Retinoic acid therapy may prevent bronchopulmonary dysplasia (BPD) by improving alveolar development in IUGR infants.
Area of Science:
- Pulmonary Medicine
- Neonatology
- Developmental Biology
Background:
- Infants with intrauterine growth retardation (IUGR) face higher risks of pulmonary complications like meconium aspiration and persistent pulmonary hypertension.
- Preterm infants with IUGR are particularly susceptible to bronchopulmonary dysplasia (BPD), characterized by underdeveloped alveoli.
- The efficacy of vitamin A in preventing BPD or death in preterm infants with IUGR is currently unknown.
Purpose of the Study:
- To investigate the impact of IUGR on lung development using a rat model.
- To determine if retinoic acid treatment can mitigate IUGR-induced lung abnormalities.
- To explore the role of retinoic acid signaling in preserving alveolar formation.
Main Methods:
- A rat model of caloric restriction was employed to simulate IUGR and study its effects on lung development.
- Lung tissue was analyzed to assess alveolar formation, elastin expression, and the activity of key signaling molecules.
- Retinoic acid treatment was administered to assess its therapeutic potential.
Main Results:
- Caloric restriction-induced alveolar hypoplasia in developing rat lungs was found to be reversible with refeeding.
- Retinoic acid treatment effectively prevented alveolar hypoplasia in the IUGR rat model.
- This protective effect was associated with increased expression of elastin and retinoic acid receptor-α, and decreased transforming growth factor-β activity.
Conclusions:
- Alveolar hypoplasia resulting from IUGR is a reversible condition.
- Retinoic acid therapy shows promise in preventing lung development issues, such as BPD, in preterm infants with IUGR.
- Further research into retinoic acid's role in managing pulmonary sequelae of IUGR is warranted.
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.
