Stanton Alice E, Goodwin Katharine, Sundarakrishnan Aswin, Jaslove Jacob M, Gleghorn Jason P, Pavlovich Amira L, Nelson Celeste M
Department of Chemical & Biological Engineering, Princeton University, Princeton, NJ, United States.
Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, United States.
Front Cell Dev Biol. 2021 Dec 1;9:725785. doi: 10.3389/fcell.2021.725785. eCollection 2021.
Mechanical forces are increasingly recognized as important determinants of cell and tissue phenotype and also appear to play a critical role in organ development. During the fetal stages of lung morphogenesis, the pressure of the fluid within the lumen of the airways is higher than that within the chest cavity, resulting in a positive transpulmonary pressure. Several congenital defects decrease or reverse transpulmonary pressure across the developing airways and are associated with a reduced number of branches and a correspondingly underdeveloped lung that is insufficient for gas exchange after birth. The small size of the early pseudoglandular stage lung and its relative inaccessibility have precluded experimental investigation of the effects of transpulmonary pressure on early branching morphogenesis. Here, we present a simple culture model to explore the effects of negative transpulmonary pressure on development of the embryonic airways. We found that negative transpulmonary pressure decreases branching, and that it does so in part by altering the expression of fibroblast growth factor 10 (). The morphogenesis of lungs maintained under negative transpulmonary pressure can be rescued by supplementing the culture medium with exogenous FGF10. These data suggest that expression is regulated by mechanical stress in the developing airways. Understanding the mechanical signaling pathways that connect transpulmonary pressure to FGF10 can lead to the establishment of novel non-surgical approaches for ameliorating congenital lung defects.
机械力越来越被认为是细胞和组织表型的重要决定因素，并且似乎在器官发育中也起着关键作用。在肺形态发生的胎儿阶段，气道腔内液体的压力高于胸腔内的压力，从而导致正的跨肺压。一些先天性缺陷会降低或逆转发育中的气道上的跨肺压，并与分支数量减少以及相应发育不全的肺相关联，这种肺在出生后不足以进行气体交换。早期假腺期肺的体积小及其相对难以接近，使得对跨肺压对早期分支形态发生影响的实验研究受到限制。在这里，我们提出了一个简单的培养模型来探索负跨肺压对胚胎气道发育的影响。我们发现负跨肺压会减少分支，并且部分是通过改变成纤维细胞生长因子10（）的表达来实现的。通过在培养基中补充外源性FGF10，可以挽救在负跨肺压下维持的肺的形态发生。这些数据表明，在发育中的气道中，（此处原文似乎不完整）的表达受机械应力调节。了解将跨肺压与FGF10联系起来的机械信号通路，可能会导致建立新的非手术方法来改善先天性肺缺陷。
