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在对抗气道疾病的斗争中看到了一线希望。

A 'tad' of hope in the fight against airway disease.

机构信息

University of Manchester, Manchester 160125, U.K.

出版信息

Biochem Soc Trans. 2020 Oct 30;48(5):2347-2357. doi: 10.1042/BST20200745.

Abstract

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.

摘要

非洲爪蟾幼体已成为研究黏液纤毛上皮的强大体内模型系统,例如人类呼吸道中的上皮。幼体皮肤具有分泌黏蛋白的细胞、运动的多纤毛细胞、离子细胞(控制局部离子动态平衡)和基底干细胞。这种细胞结构与人类肺部的大气道非常相似,是一种易于接近且可进行实验的模型系统,可用于探索黏液纤毛上皮的分子细节。幼体皮肤中的每一种细胞类型都有人类对应物,并且已经发现了用于其分化的保守基因和信号通路网络。利用非洲爪蟾模型,我们对每种细胞类型的功能有了深入的了解,这增强了我们对气道疾病的认识。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(例如基因编辑和活体成像)的不断发展,其用于了解单个细胞类型及其相互作用的用途可能会增加。例如,其体型小且遗传上易于操作,使其成为黏液纤毛表面活体成像的理想模型,尤其是在感染等环境挑战期间。此外,还可以模拟直接导致气道疾病的人类基因突变,并对针对新型治疗靶点的药物进行预筛选。

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A 'tad' of hope in the fight against airway disease.在对抗气道疾病的斗争中看到了一线希望。
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