Impaired cell–cell communication and axon guidance because of pulmonary hypoperfusion during postnatal alveolar development

Respiratory Research

Research

Qing Cui¹  Yuqing Hu¹  Jing Wang²  Sijuan Sun³  Yuan Fang⁴  Qi Sun⁵  Chuan Jiang⁵  Hao Chen⁵  Debao Li⁵  Yingying Xiao⁵  Lincai Ye⁶ 

[1] Department of Cardiology, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;Department of Infectious Diseases, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;Department of Pediatric Intensive Care Unit, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;Department of Plastic and Reconstructive Surgery, School of Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China;Department of Thoracic and Cardiovascular Surgery, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dongfang Road, 200127, Shanghai, China;Department of Thoracic and Cardiovascular Surgery, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dongfang Road, 200127, Shanghai, China;Institute of Pediatric Translational Medicine, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;Shanghai Institute for Pediatric Congenital Heart Disease, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dongfang Road, 200127, Shanghai, China;

关键词: Alveolar dysplasia;    Pulmonary hypoperfusion;    COVID-19;    Alveoli;    Congenital heart diseases;   

DOI  :  10.1186/s12931-023-02319-3

 received in 2022-09-21, accepted in 2023-01-06,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundPulmonary hypoperfusion is common in children with congenital heart diseases (CHDs) or pulmonary hypertension (PH) and causes adult pulmonary dysplasia. Systematic reviews have shown that some children with CHDs or PH have mitigated clinical outcomes with COVID-19. Understanding the effects of pulmonary hypoperfusion on postnatal alveolar development may aid in the development of methods to improve the pulmonary function of children with CHDs or PH and improve their care during the COVID-19 pandemic, which is characterized by cytokine storm and persistent inflammation.Methods and resultsWe created a neonatal pulmonary hypoperfusion model through pulmonary artery banding (PAB) surgery at postnatal day 1 (P1). Alveolar dysplasia was confirmed by gross and histological examination at P21. Transcriptomic analysis of pulmonary tissues at P7(alveolar stage 2) and P14(alveolar stage 4) revealed that the postnatal alveolar development track had been changed due to pulmonary hypoperfusion. Under the condition of pulmonary hypoperfusion, the cell–cell communication and axon guidance, which both determine the final number of alveoli, were lost; instead, there was hyperactive cell cycle activity. The transcriptomic results were further confirmed by the examination of axon guidance and cell cycle markers. Because axon guidance controls inflammation and immune cell activation, the loss of axon guidance may explain the lack of severe COVID-19 cases among children with CHDs or PH accompanied by pulmonary hypoperfusion.ConclusionsThis study suggested that promoting cell–cell communication or supplementation with guidance molecules may treat pulmonary hypoperfusion–induced alveolar dysplasia, and that COVID-19 is less likely to cause a cytokine storm in children with CHD or PH accompanied by pulmonary hypoperfusion.Graphical Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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