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Updated: Jan 10, 2026

Development of a Neonatal Piglet Acute Lung Injury Model Recreating the Early Environment of Preterm Infant Lungs
Published on: October 31, 2025
Increased pulmonary blood flow leads to alveolar dysplasia during the early postnatal developmental stage
He Zhang1, Sixie Zheng2, Zheng Wang2
1Department of Pediatric, The Affiliated Women and Children's Hospital of Ningbo University, Ningbo, Zhejiang, China.
Insights
Increased pulmonary blood flow (IncPBF) in neonates causes alveolar dysplasia, hindering lung development. A new mouse model reveals IncPBF impairs alveolar formation and function, offering insights into pediatric heart diseases.
Area of Science:
- Pediatric Cardiology
- Neonatal Lung Development
- Congenital Heart Disease Research
Background:
- Increased pulmonary blood flow (IncPBF) is linked to pulmonary arterial hypertension in children.
- Neonatal mouse models for studying IncPBF's impact on lung development are lacking.
Purpose of the Study:
- To establish a neonatal mouse model of IncPBF.
- To investigate the effects of IncPBF on postnatal lung development.
Main Methods:
- Neonatal mouse model created via abdominal aorta and inferior vena cava fistula microsurgery.
- Analysis included ultrasound, hematoxylin-eosin staining, immunostaining, and RNA-sequencing.
- Investigated the role of Mfap5-positive myofibroblasts and Shh-Gli1 signaling.
Main Results:
- IncPBF significantly reduced alveolarization and markers for alveolar type 1 (AT1) and type 2 (AT2) cells.
- Gene expression analysis revealed downregulation of angiogenesis, cell migration, and lipid metabolism pathways.
- Suppression of specific signaling pathways ameliorated IncPBF-induced alveolar hypoplasia.
Conclusions:
- IncPBF causes alveolar dysplasia in early development.
- A validated neonatal mouse model for IncPBF was successfully created.
- This model serves as a platform for studying IncPBF-associated pediatric diseases.
Background:
Increased pulmonary blood flow (IncPBF), one of the most important features of many children with congenital heart diseases, is well-known as a prerequisite for the induction of pulmonary arterial hypertension. However, due to the lack of neonatal mouse models of IncPBF, it remains largely unknown how IncPBF affects postnatal lung development.
Methods And Results:
A neonatal mouse model of IncPBF was created via abdominal aorta and inferior vena cava fistula microsurgery at postnatal day 7 (P7) and verified by abdominal ultrasound and cardiac ultrasound. Hematoxylin-eosin staining demonstrated that at P14, the number of alveoli was significantly reduced in the IncPBF group compared with the sham group. Immunostaining further confirmed the results, showing that the markers of alveoli type 1 (AT1), alveoli type 2 (AT2), and endothelial cells were significantly reduced in the IncPBF group compared with the sham group. Moreover, RNA-sequencing analysis demonstrated a substantial difference of gene expression profile between IncPBF and sham lungs, and many gene ontology terms or reactome enrichment that are associated with normal alveolar development and pulmonary function, such as angiogenesis, cell migration, and lipid metabolism, were downregulated. Mechanistically, suppression of Mfap5-positive myofibroblasts or Shh-Gli1 signaling could ameliorate IncPBF-induced alveolar hypoplasia.
Conclusions:
IncPBF led to alveolar dysplasia during the early developmental stage, and a neonatal mouse model of IncPBF was successfully created. This study introduced a platform for understanding IncPBF-associated pediatric diseases.
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