Epidermal growth factor induced macropinocytosis directs branch formation of lung epithelial cells
Epidermal growth factor induced macropinocytosis directs branch formation of lung epithelial cells
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DOI：
10.1016/j.bbrc.2018.11.028
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发表时间：
2018-12-09
影响因子：
3.1
通讯作者：
Nakase, Ikuhiko
中科院分区：
文献类型：
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作者：
Hagiwara, Masaya;Nakase, Ikuhiko
肺分支形态发生是一个复杂的系统，涉及许多分子相互作用来填充三维空间，但其潜在的发育机制仍不完全清楚。本文采用体外实验和数学模拟的方法，研究了表皮生长因子(EGF)对正常人支气管上皮细胞及其三维(3D)分支模式形成的影响。结果表明，EGF是3D分枝模式形成所必需的，其受体在分枝顶端高表达，为细胞迁移提供驱动力。由EGFR表达引起的巨噬细胞吞噬与枝条顶端的营养吸收密切相关。我们对人类肺细胞有效分枝形成的发现有助于进一步了解器官发生的分子机制，这些重要机制也可能参与相关的肺部疾病，如畸形。(C)2018 Elsevier Inc.保留所有权利。
Lung branching morphogenesis is a complex system involving many molecular interactions to filling the three dimensional spaces; however, the underlying developmental mechanisms are still not fully understood. In this paper, we have investigated the effect of epidermal growth factor (EGF) on normal human bronchial epithelial cells and their three-dimensional (3D) branching pattern formation by using in vitro experiments and mathematical simulation. The results show that EGF is essential for 3D branch pattern formation and its receptor is highly expressed at the tip of branches to generate the drive force for cells to migrate. Macropinocytosis induced by EGFR expression is firmly contributed to the nutrition uptake at the tip of branches. Our findings for effective branching formation of human lung cells contribute to further understanding molecular mechanisms of organogenesis, and the important mechanisms also possibly participate in related lung disease such as malformation. (C) 2018 Elsevier Inc. All rights reserved.