Molecular mechanisms of alveolar development and regeneration

项目总结/摘要 本申请旨在阐明发育过程中肺泡形成的分子机制， 对肺损伤的反应。我们期望我们的研究将提供新的见解人类的发病机制， 由于肺泡发育或再生失败而引起的肺部疾病，特别是支气管肺炎 慢性阻塞性肺疾病（COPD）。在初步研究中， 发现了平面细胞极性（PCP）在控制肺泡形成中的关键作用。在这份提案中，我们的目标是 为了测试PCP信号传导如何介导肺泡细胞和间充质细胞之间的细胞-细胞相互作用， 肌成纤维细胞，导致PDGF信号传导、细胞形状变化和肺泡形成。我们的具体目标是： (1)为了检验Vangl 2介导的平面细胞极性是PDGF信号传导和细胞凋亡所需的假设， （2）为了验证Wnt 5a-Vangl 2轴在发育过程中的形态变化， 控制肺泡形成;和（3）在成人肺损伤后的分子特征。 总而言之，这些研究将增加我们对肺泡形成的机械理解 发展和肺损伤后，并促进未来的诊断和治疗肺部疾病引起的 失去了肺泡

Project Summary/Abstract This application aims to elucidate the molecular mechanisms of alveolar formation during development and in response to lung injury. We anticipate that our study will provide new insight into the pathogenesis of human lung diseases caused by the failure of alveolar development or regeneration, notably bronchopulmonary dysplasia (BPD) and chronic obstructive lung disease (COPD), respectively. In preliminary studies, we have discovered a critical role of planar cell polarity (PCP) in controlling alveolar formation. In this proposal, we aim to test how PCP signaling mediates cell-cell interactions between alveolar cells and mesenchymal myofibroblasts, leading to PDGF signaling, cell shape changes and alveolar formation. Our specific aims are: (1) To test the hypothesis that Vangl2-mediated planar cell polarity is required for PDGF signaling and cell shape changes during alveolar formation in development; (2) To test the hypothesis that a Wnt5a-Vangl2 axis controls alveolar formation; and (3) To molecularly characterize realveolarization following lung injury in adults. Taken together, these studies will increase our mechanistic understanding of alveolar formation during development and following lung injury and facilitate future diagnosis and treatment of lung diseases caused by loss of alveoli.