Loss of microRNA-30a and sex-specific effects on the neonatal hyperoxic lung injury.

Autor: Grimm SL; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.; Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX, USA.; Molecular and Cellular Biology Department, Baylor College of Medicine, Houston, TX, USA., Reddick S; Vanderbilt University School of Medicine, Nashville, TN, USA., Dong X; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Leek C; Department of Pediatrics, Division of Neonatology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA., Wang AX; Department of Pediatrics, Division of Neonatology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA., Gutierrez MC; Department of Pediatrics, Division of Neonatology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA., Hartig SM; Molecular and Cellular Biology Department, Baylor College of Medicine, Houston, TX, USA.; Department of Medicine, Division of Endocrinology, Baylor College of Medicine, Houston, TX, USA., Moorthy B; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Coarfa C; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA. coarfa@bcm.edu.; Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX, USA. coarfa@bcm.edu.; Molecular and Cellular Biology Department, Baylor College of Medicine, Houston, TX, USA. coarfa@bcm.edu., Lingappan K; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. lingappank@chop.edu.; Department of Pediatrics, Division of Neonatology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA. lingappank@chop.edu.
Jazyk: angličtina
Zdroj: Biology of sex differences [Biol Sex Differ] 2023 Aug 08; Vol. 14 (1), pp. 50. Date of Electronic Publication: 2023 Aug 08.
DOI: 10.1186/s13293-023-00535-6
Abstrakt: Background: Bronchopulmonary dysplasia (BPD) is characterized by an arrest in lung development and is a leading cause of morbidity in premature neonates. It has been well documented that BPD disproportionally affects males compared to females, but the molecular mechanisms behind this sex-dependent bias remain unclear. Female mice show greater preservation of alveolarization and angiogenesis when exposed to hyperoxia, accompanied by increased miR-30a expression. In this investigation, we tested the hypothesis that loss of miR-30a would result in male and female mice experiencing similar impairments in alveolarization and angiogenesis under hyperoxic conditions.
Methods: Wild-type and miR-30a -/- neonatal mice were exposed to hyperoxia [95% FiO 2 , postnatal day [PND1-5] or room air before being euthanized on PND21. Alveolarization, pulmonary microvascular development, differences in lung transcriptome, and miR-30a expression were assessed in lungs from WT and miR-30a -/- mice of either sex. Blood transcriptomic signatures from preterm newborns (with and without BPD) were correlated with WT and miR-30a -/- male and female lung transcriptome data.
Results: Significantly, the sex-specific differences observed in WT mice were abrogated in the miR-30a -/- mice upon exposure to hyperoxia. The loss of miR-30a expression eliminated the protective effect in females, suggesting that miR-30a plays an essential role in regulating alveolarization and angiogenesis. Transcriptome analysis by whole lung RNA-Seq revealed a significant response in the miR-30a -/- female hyperoxia-exposed lung, with enrichment of pathways related to cell cycle and neuroactive ligand-receptor interaction. Gene expression signature in the miR-30a -/- female lung associated with human BPD blood transcriptomes. Finally, we showed the spatial localization of miR-30a transcripts in the bronchiolar epithelium.
Conclusions: miR-30a could be one of the biological factors mediating the resilience of the female preterm lung to neonatal hyperoxic lung injury. A better understanding of the effects of miR-30a on pulmonary angiogenesis and alveolarization may lead to novel therapeutics for treating BPD.
(© 2023. Society for Women's Health Research and BioMed Central Ltd.)
Databáze: MEDLINE
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