Impaired cell-cell communication and axon guidance because of pulmonary hypoperfusion during postnatal alveolar development.
Impaired cell-cell communication and axon guidance because of pulmonary hypoperfusion during postnatal alveolar development.
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DOI：
10.1186/s12931-023-02319-3
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发表时间：
2023-01-11
影响因子：
5.8
通讯作者：
中科院分区：
文献类型：
--
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肺灌注不足在先天性心脏病（CHD）或肺动脉高压（PH）儿童中很常见，并导致成人肺发育不良。系统性综述表明，一些患有CHD或PH的儿童缓解了COVID-19的临床结局。了解肺灌注不足对出生后肺泡发育的影响可能有助于开发改善CHD或PH儿童肺功能的方法，并改善COVID-19大流行期间的护理，其特征是细胞因子风暴和持续炎症。我们在出生后第1天（P1）通过肺动脉结扎术（PAB）建立了新生儿肺低灌注模型。在P21时通过大体和组织学检查证实肺泡发育不良。P7（肺泡2期）和P14（肺泡4期）肺组织的转录组学分析显示，由于肺灌注不足，出生后肺泡发育轨迹发生了变化。在肺灌注不足的条件下，细胞间通讯和轴突导向，这两者都决定了肺泡的最终数量，失去了;相反，有过度活跃的细胞周期活动。通过轴突导向和细胞周期标志物的检查进一步证实了转录组学结果。由于轴突导向控制炎症和免疫细胞活化，轴突导向的丧失可能解释了伴有肺灌注不足的CHD或PH儿童中缺乏严重COVID-19病例的原因。这项研究表明，促进细胞间通讯或补充引导分子可能治疗肺灌注不足引起的肺泡发育不良，并且COVID-19不太可能在伴有肺灌注不足的CHD或PH儿童中引起细胞因子风暴。在线版本包含补充材料，可通过10.1186/s12931-023-02319-3获得。
Pulmonary 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. We 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. This 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. The online version contains supplementary material available at 10.1186/s12931-023-02319-3.
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