Negative Transpulmonary Pressure Disrupts Airway Morphogenesis by Suppressing Fgf10.
Negative Transpulmonary Pressure Disrupts Airway Morphogenesis by Suppressing Fgf10.
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DOI：
10.3389/fcell.2021.725785
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发表时间：
2021
影响因子：
5.5
通讯作者：
Nelson CM
中科院分区：
文献类型：
--
作者：
Stanton AE;Goodwin K;Sundarakrishnan A;Jaslove JM;Gleghorn JP;Pavlovich AL;Nelson CM
机械力越来越被认为是细胞和组织表型的重要决定因素，也似乎在器官发育中发挥着关键作用。在肺形态发生的胎儿期，气道腔内液体的压力高于胸腔内液体的压力，从而产生正的经肺压力。几种先天性缺陷降低或逆转了整个发育中的呼吸道的跨肺压，并与分支数量减少和相应的肺不发达相关，出生后肺不足以进行气体交换。早期假腺期肺的体积较小，在宫内相对难以接近，这使得经肺压力对早期分支形态发生的影响的实验研究变得困难。在这里，我们提出了一个简单的培养模型，以探索负的跨肺压力对胚胎呼吸道发育的影响。我们发现，负的跨肺压减少了分支，这部分是通过改变成纤维细胞生长因子10(Fgf10)的表达来实现的。加入外源性FGF10可以挽救负压下肺的形态发生。这些数据表明，Fgf10的表达受发育中的呼吸道机械应力的调节。了解连接经肺压力和FGF10的机械信号通路有助于建立改善先天性肺缺陷的新的非手术方法。
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 in utero 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 (Fgf10). The morphogenesis of lungs maintained under negative transpulmonary pressure can be rescued by supplementing the culture medium with exogenous FGF10. These data suggest that Fgf10 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.
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DOI：
10.1002/path.5188
发表时间：
2019-03
期刊：
The Journal of pathology
影响因子：
--
作者：
Danopoulos S;Thornton ME;Grubbs BH;Frey MR;Warburton D;Bellusci S;Al Alam D
通讯作者：
Al Alam D
DOI：
10.1152/ajplung.2000.279.6.l1159
发表时间：
2000-12-01
影响因子：
4.9
作者：
Guilbert, TW;Gebb, SA;Shannon, JM
通讯作者：
Shannon, JM
影响因子：
2.4
作者：
ADZICK, NS;HARRISON, MR;FINKBEINER, W
通讯作者：
FINKBEINER, W
DOI：
10.1016/0034-5687(67)90035-7
发表时间：
1967-01-01
期刊：
RESPIRATION PHYSIOLOGY
影响因子：
--
作者：
ADAMS, FH;DESILETS, DT;TOWERS, B
通讯作者：
TOWERS, B
影响因子：
2.2
作者：
Baird, Robert;Ehan, Nasir;Laberge, Jean-Martin
通讯作者：
Laberge, Jean-Martin