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Published on: September 16, 2020
Effects of retinoic acid on airspace development and lung collagen in hyperoxia-exposed newborn rats
K A Veness-Meehan1, F G Bottone, A D Stiles
1Department of Pediatrics, Division of Neonatal-Perinatal Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7596, USA.
Insights
Retinoic acid did not improve lung septation in newborn rats exposed to hyperoxia, a model for bronchopulmonary dysplasia. However, it increased collagen and improved survival, suggesting benefits for hyperoxia-induced lung injury.
Area of Science:
- Neonatal lung development
- Pulmonary medicine
- Toxicology
Background:
- Bronchopulmonary dysplasia (BPD) involves impaired lung septation and alveolarization due to hyperoxic injury.
- Dexamethasone, used in neonatal care, also hinders lung development.
- Vitamin A and retinoic acid show potential in mitigating BPD.
Purpose of the Study:
- To investigate if retinoic acid treatment during hyperoxia exposure improves septal formation in a neonatal rat model.
- To assess retinoic acid's effects on lung structure and collagen in hyperoxia-induced lung injury.
Main Methods:
- Newborn rats were exposed to hyperoxia (≥90% O2) from postnatal day 3 to 14.
- Rats received retinoic acid and/or dexamethasone treatments during specific periods.
- Lung septation, airspace size, collagen content, and survival rates were evaluated.
Main Results:
- Retinoic acid did not improve septal formation or reduce airspace size in hyperoxia-exposed rats.
- Retinoic acid increased collagen in lung airspace walls, likely via posttranscriptional regulation.
- Combined retinoic acid and dexamethasone therapy showed the greatest improvement in animal survival.
Conclusions:
- Retinoic acid does not prevent hyperoxia-induced impairment of lung septation or alveolarization.
- Retinoic acid may offer benefits in hyperoxia-induced lung injury and affects lung matrix.
- Further research is needed to understand retinoic acid's role in neonatal lung injury and repair.
Abstract:
Impaired septal formation and decreased alveolarization are often caused by hyperoxic injury to the developing lung and are characteristic features of bronchopulmonary dysplasia. Dexamethasone, frequently administered to infants during oxygen exposure, also inhibits septal formation in the newborn lung. Vitamin A administration reduces the incidence of bronchopulmonary dysplasia in vitamin A-deficient premature infants, and retinoic acid improves alveolarization in newborn rats treated with dexamethasone, indicating that retinoic acid may be useful in preventing hyperoxia-induced impaired septation in bronchopulmonary dysplasia. To investigate whether treatment with retinoic acid during exposure to hyperoxia would improve septal formation, newborn rats exposed to > or =90% O(2) from d 3 of life to d 14 were treated with retinoic acid (d 3-13 of life) and/or dexamethasone (d 4-13 of life). In contrast with the effects of retinoic acid on dexamethasone-induced inhibition of alveolarization, we found that retinoic acid did not improve septal formation or decrease airspace size in animals exposed to hyperoxia alone or to hyperoxia plus dexamethasone. Retinoic acid did, however, increase collagen in airspace walls as demonstrated by staining and immunohistochemistry. There was no increase in procollagen mRNA by Northern hybridization analysis, indicating that retinoic acid-associated increases in lung collagen are likely due to posttranscriptional regulation. There was a trend toward increased survival in hyperoxia in animals treated with retinoic acid to the extent that combined therapy with retinoic acid and dexamethasone resulted in the greatest improvement in animal survival. These results suggest that although retinoic acid may be of benefit in hyperoxia-induced lung injury and may have important effects on lung matrix, it does not prevent impairment of septation or induce alveolar formation during exposure to hyperoxia.