Smooth Muscle Differentiation Is Essential for Airway Size, Tracheal Cartilage Segmentation, but Dispensable for Epithelial Branching.
Smooth Muscle Differentiation Is Essential for Airway Size, Tracheal Cartilage Segmentation, but Dispensable for Epithelial Branching.
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DOI：
10.1016/j.devcel.2020.02.001
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发表时间：
2020-04-06
影响因子：
11.8
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Young RE;Jones MK;Hines EA;Li R;Luo Y;Shi W;Verheyden JM;Sun X
气道平滑肌最为人所知的是它在哮喘等疾病中作为气道收缩剂的作用。然而，其在肺发育中的功能仍有争议。一个流行的模型，由体外数据支持，假设气道平滑肌促进肺分支通过蠕动和推动腔内液体到分支尖端。在这里，我们通过失活心肌蛋白来验证该模型，心肌蛋白可以阻止气道平滑肌分化。我们发现心肌蛋白突变体显示正常分支，尽管没有蠕动。相反，气管软骨、脉管系统和神经支配模式均被破坏。此外，在突变体中，气道直径减小，与预期相反，没有平滑肌收缩会导致更放松，从而更宽的气道。这些结果共同表明，在发育过程中，虽然气道平滑肌对上皮分支是必不可少的，但它对于建立气管结构和促进气道生长是不可或缺的。Young等人发现气道平滑肌的分化并不是体内肺分支形态发生所必需的。然而，它对于气管结构的正确形成是必不可少的，包括软骨图案。此外，它对促进气道大小至关重要。
Airway smooth muscle is best known for its role as an airway constrictor in diseases such as asthma. However, its function in lung development is debated. A prevalent model, supported by in vitro data, posits that airway smooth muscle promotes lung branching through peristalsis and pushing intraluminal fluid to branching tips. Here, we test this model in vivo by inactivating Myocardin, which prevented airway smooth muscle differentiation. We found that Myocardin mutants show normal branching, despite absence of peristalsis. In contrast, tracheal cartilage, vasculature, and neural innervation patterns were all disrupted. Furthermore, airway diameter is reduced in the mutant, counter to the expectation that the absence of smooth muscle constriction would lead to a more relaxed and thereby wider airway. These findings together demonstrate that during development, while airway smooth muscle is dispensable for epithelial branching, it is integral for building the tracheal architecture and promoting airway growth. Young et al. find that the differentiation of airway smooth muscle is not required for lung branching morphogenesis in vivo. However, it is essential for the proper formation of tracheal architecture including cartilage patterning. In addition, it is essential for promoting airway size.
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影响因子：
14.9
作者：
Babicki S;Arndt D;Marcu A;Liang Y;Grant JR;Maciejewski A;Wishart DS
通讯作者：
Wishart DS
影响因子：
11.8
作者：
Kim HY;Pang MF;Varner VD;Kojima L;Miller E;Radisky DC;Nelson CM
通讯作者：
Nelson CM
DOI：
10.1242/dev.163014
发表时间：
2018-05-11
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Chung MI;Bujnis M;Barkauskas CE;Kobayashi Y;Hogan BLM
通讯作者：
Hogan BLM
影响因子：
16.6
作者：
Kishimoto K;Tamura M;Nishita M;Minami Y;Yamaoka A;Abe T;Shigeta M;Morimoto M
通讯作者：
Morimoto M
影响因子：
4.6
作者：
Mailleux, AA;Kelly, R;Bellusci, S
通讯作者：
Bellusci, S