2. Academic Validation
  3. Increased pulmonary blood flow leads to alveolar dysplasia during the early postnatal developmental stage

Increased pulmonary blood flow leads to alveolar dysplasia during the early postnatal developmental stage

  • Cell Biosci. 2025 Nov 24;15(1):161. doi: 10.1186/s13578-025-01502-x.
He Zhang # 1,  Sixie Zheng # 2,  Zheng Wang 2,  Yingying Xiao 3,  Yuqing Hu 3,  Debao Li 4,  Qing Cui 3,  Chenxi Liu 3,  Yiting Xue 2,  Junhua Wu 5,  Sijuan Sun 6,  Lincai Ye 7 8
Affiliations

Affiliations

  • 1 Department of Pediatric, The Affiliated Women and Children's Hospital of Ningbo University, Ningbo, Zhejiang, China.
  • 2 Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 Department of Pediatric Surgery, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
  • 5 Department of Pediatric, The Affiliated Women and Children's Hospital of Ningbo University, Ningbo, Zhejiang, China. [email protected].
  • 6 Department of Pediatric Intensive Care Unit, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai, 200127, China. [email protected].
  • 7 Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 8 Shanghai Institute for Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai, 200127, China. [email protected].
  • # Contributed equally.
PMID: 41287066 DOI: 10.1186/s13578-025-01502-x
Abstract

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.

Keywords

Animal models; Congenital heart diseases; Increased pulmonary blood flow; Lung; Pulmonary dysplasia.

Figures
Products