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.

Cell & Bioscience
|November 25, 2025
PubMed

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.
Abstract

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