Loss of E-cadherin is causal to pathologic changes in chronic lung disease.
Loss of E-cadherin is causal to pathologic changes in chronic lung disease.
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DOI：
10.1038/s42003-022-04150-w
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发表时间：
2022-10-29
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
上皮细胞排列在肺粘膜表面，是抵御环境侮辱毒性暴露的第一道防线，它们的完整性对肺健康至关重要。在慢性阻塞性肺疾病(COPD)患者的肺上皮细胞中，早期发现的是黏附连接蛋白的关键成分E-钙粘附素的丢失。这种下降的原因尚不清楚，可能是由于管腔内的侮辱或小气道的结构变化。无论如何，尚不清楚E-钙粘附素的缺失是疾病的标志还是驱动因素。在此，我们报告E-钙粘附素的丢失是慢性肺部疾病发展的原因。利用细胞类型特异性启动子，我们发现在成年小鼠模型中，E-钙粘附素在II型肺泡上皮细胞中被敲除，而在I型细胞中不被敲除，导致肺泡扩大。此外，E-钙粘附素在呼吸道纤毛细胞中的敲除，而不是在球状细胞中的敲除，增加了呼吸道的高反应性。我们证明，上调E-钙粘附素的策略挽救了单层完整性，并作为潜在的治疗靶点。肺泡上皮和呼吸道纤毛细胞中黏附连接蛋白E-钙粘附素的特异性丢失导致慢性肺部疾病。
Epithelial cells line the lung mucosal surface and are the first line of defense against toxic exposures to environmental insults, and their integrity is critical to lung health. An early finding in the lung epithelium of patients with chronic obstructive pulmonary disease (COPD) is the loss of a key component of the adherens junction protein called E-cadherin. The cause of this decrease is not known and could be due to luminal insults or structural changes in the small airways. Irrespective, it is unknown whether the loss of E-cadherin is a marker or a driver of disease. Here we report that loss of E-cadherin is causal to the development of chronic lung disease. Using cell-type-specific promoters, we find that knockout of E-cadherin in alveolar epithelial type II but not type 1 cells in adult mouse models results in airspace enlargement. Furthermore, the knockout of E-cadherin in airway ciliated cells, but not club cells, increase airway hyperreactivity. We demonstrate that strategies to upregulate E-cadherin rescue monolayer integrity and serve as a potential therapeutic target. Specific loss of the adherens junction protein E-cadherin in alveolar epithelial and airway ciliated cells causes chronic lung disease.
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影响因子：
6
作者：
通讯作者：
--
影响因子：
5.8
作者：
Boxio R;Wartelle J;Nawrocki-Raby B;Lagrange B;Malleret L;Hirche T;Taggart C;Pacheco Y;Devouassoux G;Bentaher A
通讯作者：
Bentaher A
DOI：
10.1152/ajplung.00115.2016
发表时间：
2016-08-01
影响因子：
4.9
作者：
Kulkarni, Tejaswini;de Andrade, Joao;Thannickal, Victor J.
通讯作者：
Thannickal, Victor J.
影响因子：
4.8
作者：
Forteza, Rosanna Malbran;Casalino-Matsuda, S. Marina;Monzon, Maria E.
通讯作者：
Monzon, Maria E.
影响因子：
3.1
作者：
Ghosh, Baishakhi;Reyes-Caballero, Hermes;Sidhaye, Venkataramana K.
通讯作者：
Sidhaye, Venkataramana K.