A 'tad' of hope in the fight against airway disease.
A 'tad' of hope in the fight against airway disease.
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DOI：
10.1042/bst20200745
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发表时间：
2020-10-30
影响因子：
3.9
通讯作者：
Dubaissi E
中科院分区：
文献类型：
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作者：
Dubaissi E
非洲爪蟾蝌蚪已经成为一个强大的体内模型系统，以研究粘膜纤毛上皮细胞，如那些在人类气道。蝌蚪的皮肤有粘液分泌细胞、能动的多纤毛细胞、离子细胞（控制局部离子稳态）和基底干细胞。这种细胞结构与人肺的大气道非常相似，代表了一种易于获得和实验上易于处理的模型系统，以探索粘膜纤毛上皮细胞的分子细节。蝌蚪皮肤中的每一种细胞类型都有一个人类等价物，并且已经发现了一个保守的基因网络和它们分化的信号通路。使用非洲爪蟾模型已经实现了对每种细胞类型功能的深入了解，这增强了我们对气道疾病的理解。这个简单的模型已经对该领域产生了深远的影响，但是随着分子技术（例如基因编辑和实时成像）的不断发展，它在理解单个细胞类型及其相互作用方面的应用可能会增加。例如，它的小尺寸和遗传易处理性使其成为粘液纤毛表面的实时成像的理想模型，特别是在环境挑战如感染期间。进一步的潜力存在于模拟直接导致气道疾病的人类基因突变和针对新的治疗靶点的药物的预筛选。
Xenopus tadpoles have emerged as a powerful in vivo model system to study mucociliary epithelia such as those found in the human airways. The tadpole skin has mucin-secreting cells, motile multi-ciliated cells, ionocytes (control local ionic homeostasis) and basal stem cells. This cellular architecture is very similar to the large airways of the human lungs and represents an easily accessible and experimentally tractable model system to explore the molecular details of mucociliary epithelia. Each of the cell types in the tadpole skin has a human equivalent and a conserved network of genes and signalling pathways for their differentiation has been discovered. Great insight into the function of each of the cell types has been achieved using the Xenopus model and this has enhanced our understanding of airway disease. This simple model has already had a profound impact on the field but, as molecular technologies (e.g. gene editing and live imaging) continue to develop apace, its use for understanding individual cell types and their interactions will likely increase. For example, its small size and genetic tractability make it an ideal model for live imaging of a mucociliary surface especially during environmental challenges such as infection. Further potential exists for the mimicking of human genetic mutations that directly cause airway disease and for the pre-screening of drugs against novel therapeutic targets.