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Hyperoxia-induced miR-342-5p down-regulation exacerbates neonatal bronchopulmonary dysplasia via the Raf1 regulator Spred3.
- Source :
-
British Journal of Pharmacology . Jun2021, Vol. 178 Issue 11, p2266-2283. 18p. 1 Color Photograph, 6 Graphs. - Publication Year :
- 2021
-
Abstract
- <bold>Background and Purpose: </bold>Bronchopulmonary dysplasia (BPD) is the most prevalent chronic paediatric lung disease and is linked to the development of chronic obstructive pulmonary disease. MicroRNA-based regulation of type II alveolar epithelial cell (T2AEC) proliferation and apoptosis is an important factor in the pathogenesis of BPD and warrants further investigation.<bold>Experimental Approach: </bold>Two murine models of hyperoxic lung injury (with or without miR-342-5p or Sprouty-related, EVH1 domain-containing protein 3 [Spred3] modulation) were employed: a hyperoxia-induced acute lung injury model (100% O2 on postnatal days 1-7) and the BPD model (100% O2 on postnatal days 1-4, followed by room air for 10 days). Tracheal aspirate pellets from healthy control and moderate/severe BPD neonates were randomly selected for clinical miR-342-5p analysis.<bold>Key Results: </bold>Hyperoxia decreased miR-342-5p levels in primary T2AECs, MLE12 cells and neonatal mouse lungs. Transgenic miR-342 overexpression in neonatal mice ameliorated survival rates and improved the BPD phenotype and BPD-associated pulmonary arterial hypertension (PAH). T2AEC-specific miR-342 transgenic overexpression, as well as miR-342-5p mimic therapy, also ameliorated the BPD phenotype and associated PAH. miR-342-5p targets the 3'UTR of the Raf1 regulator Spred3, inhibiting Spred3 expression. Treatment with recombinant Spred3 exacerbated the BPD phenotype and associated PAH. Notably, miR-342-5p inhibition under room air conditions did not mimic the BPD phenotype. Moderate/severe BPD tracheal aspirate pellets exhibited decreased miR-342-5p levels relative to healthy control pellets.<bold>Conclusion and Implications: </bold>These findings suggest that miR-342-5p mimic therapy may show promise in the treatment or prevention of BPD. [ABSTRACT FROM AUTHOR]
- Subjects :
- *BRONCHOPULMONARY dysplasia
*OBSTRUCTIVE lung diseases
*SURVIVAL rate
*PHENOTYPES
*LUNG diseases
*BIOCHEMISTRY
*BIOLOGICAL models
*ANIMAL populations
*RESEARCH
*LUNGS
*ANIMAL experimentation
*RESEARCH methodology
*RNA
*MEDICAL cooperation
*EVALUATION research
*PHENOMENOLOGY
*COMPARATIVE studies
*HYPEROXIA
*MICE
Subjects
Details
- Language :
- English
- ISSN :
- 00071188
- Volume :
- 178
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- British Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 150293425
- Full Text :
- https://doi.org/10.1111/bph.15371