Breakdown of Epithelial Barrier Integrity and Overdrive Activation of Alveolar Epithelial Cells in the Pathogenesis of Acute Respiratory Distress Syndrome and Lung Fibrosis.
Breakdown of Epithelial Barrier Integrity and Overdrive Activation of Alveolar Epithelial Cells in the Pathogenesis of Acute Respiratory Distress Syndrome and Lung Fibrosis.
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DOI：
10.1155/2015/573210
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发表时间：
2015
影响因子：
--
通讯作者：
Nakazato M
中科院分区：
文献类型：
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作者：
Yanagi S;Tsubouchi H;Miura A;Matsumoto N;Nakazato M
单个肺泡上皮细胞（AEC）协作形成大气和充满液体的组织之间的紧密屏障，以实现正常的气体交换。AEC的紧密连接提供了细胞间的密封，并且是维持AEC屏障完整性的组成部分。AEC屏障重建的破坏和失败导致灾难性的后果，导致肺泡洪水和随后的破坏性纤维化瘢痕。最近的证据表明，许多纤维化肺疾病涉及AEC作为损伤的常见目标和作为正在进行的病理过程的驱动器。异常活化的AEC表达负责成纤维细胞增殖、迁移和活化的大多数生长因子和趋化因子。目前的证据表明，AECs可能通过几种机制在纤维化的初始步骤中获得活化，包括发育途径的异常重演，上皮完整性所必需的分子的缺陷，以及老化相关特性的加速。在这些初始触发事件中，上皮Pten（一种负调节PI 3 K/Akt通路并且对肺发育至关重要的多重磷酸酶）通过调节损伤后AEC屏障完整性对于预防肺泡泛洪和肺纤维化是必不可少的。AEC屏障完整性的重建还涉及特化干/祖细胞的部署。
Individual alveolar epithelial cells (AECs) collaboratively form a tight barrier between atmosphere and fluid-filled tissue to enable normal gas exchange. The tight junctions of AECs provide intercellular sealing and are integral to the maintenance of the AEC barrier integrity. Disruption and failure of reconstitution of AEC barrier result in catastrophic consequences, leading to alveolar flooding and subsequent devastating fibrotic scarring. Recent evidences reveal that many of the fibrotic lung diseases involve AECs both as a frequent target of injury and as a driver of ongoing pathological processes. Aberrantly activated AECs express most of the growth factors and chemokines responsible for the proliferation, migration, and activation of fibroblasts. Current evidences suggest that AECs may acquire overdrive activation in the initial step of fibrosis by several mechanisms, including abnormal recapitulation of the developmental pathway, defects of the molecules essential for epithelial integrity, and acceleration of aging-related properties. Among these initial triggering events, epithelial Pten, a multiple phosphatase that negatively regulates the PI3K/Akt pathway and is crucial for lung development, is essential for the prevention of alveolar flooding and lung fibrosis through the regulation of AEC barrier integrity after injury. Reestablishment of AEC barrier integrity also involves the deployment of specialized stem/progenitor cells.