CircABPD1 alleviates oxidative lung injury of bronchopulmonary dysplasia through regulating miR-330-3p/HIF1α axis
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Updated: Jul 17, 2025
Isolation of Pulmonary Artery Smooth Muscle Cells from Neonatal Mice
Published on: October 19, 2013
1School of Pediatrics, Nanjing Medical University, Nanjing, Jiangsu, China; Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, China.
Insights
Human milk exosomes contain circABPD1, a circular RNA that may prevent bronchopulmonary dysplasia (BPD). This study shows circABPD1 improves lung structure and function in BPD models by targeting miR-330-3p and HIF1α.
Area of Science:
- Neonatal Medicine
- Molecular Biology
- Respiratory Medicine
Background:
- Bronchopulmonary dysplasia (BPD) is a common respiratory complication in preterm infants.
- Human milk components, particularly exosomes, show therapeutic potential for BPD.
- Circular RNAs within exosomes are implicated in cellular regulation, but their role in BPD is unknown.
Purpose of the Study:
- To investigate the role and mechanism of human milk exosome-derived circABPD1 in preventing BPD.
- To explore circABPD1's potential as a therapeutic agent for BPD.
Main Methods:
- Established in vivo and in vitro models of BPD using hyperoxia exposure.
- Verified the properties and effects of circABPD1 through overexpression and rescue experiments.
- Investigated the molecular mechanism involving miR-330-3p and HIF1α.
Main Results:
- Overexpression of circABPD1 improved alveolar structure and reduced lung injury in BPD models.
- circABPD1 promoted cell proliferation and reduced oxidative stress in lung epithelial cells.
- Mechanistically, circABPD1 targets miR-330-3p to regulate HIF1α expression.
Conclusions:
- circABPD1, delivered via human milk exosomes, ameliorates BPD pathology.
- The miR-330-3p/HIF1α axis is a key pathway through which circABPD1 exerts its protective effects.
- circABPD1 represents a novel therapeutic target for preventing and treating BPD.
Abstract:
In the NICU, bronchopulmonary dysplasia (BPD) is a concerning common respiratory complication in preterm and low birth-weight infants. Clinical studies have confirmed that human milk has an important nutritional role for children with BPD, therefore, dentification of beneficial components in human milk that prevent BPD is urgently needed. Our previous work showed that human milk exosomes (HM-Exos) could inhibit apoptosis of alveolar type II epithelial cells (AT II), and the circular RNA (circRNA)-circABPD1 were highly expressed in preterm colostrum milk exosomes. Exosomes transport circRNAs that are stable and may exert anti-inflammatory and immune effects attracted the attention of researchers, but the role and mechanism of human milk exosome-derived circABPD1 in BPD remains unclear. Here, we constructed BPD in vivo and in vitro models through exposure to hyperoxia, verified the effect of circABPD1 and revealed its mechanism through rescue experiments. We found that circABPD1 had circRNA properties, and overexpression of circABPD1 could improve reduced alveolar number, enlarged the alveolar linear intercept in vivo models of BPD, promote cell proliferation, reduce oxidative stress levels and alleviate lung epithelial cell damage in vivo and in vitro models. Mechanistically, circABPD1 targets miR-330-3p and regulates the expression of HIF1α. These results suggest that circABPD1 can improve the pathologoical changes of bronchopulmonary dysplasia, promote cell proliferation, inhibit oxidative stress level, and alleviate lung injury by targeting the miR-330-3p/HIF1α axis, which provides a new idea for the prevention and treatment of bronchopulmonary dysplasia.
