Notch 信号通路在上皮细胞生理、病理过程中发挥重要作用，且对骨髓间充质 干细胞（MSCs）有关键性调控作用。在前期研究中我们发现 Notch 信号通路与 MSCs 的自我更新和分化潜能密切相关，也发现 COPD 大鼠气道上皮细胞、Ⅱ型肺泡上皮细胞 Notch 信号通路下调。本课题将进一步研究 Notch1 调控 MSCs 自我更新和分化潜能的机制；Notch1 诱导性 MSCs 与 COPD 大鼠受损气道上皮细胞、Ⅱ型肺泡上皮细胞体外共培养，研究其对受损上皮细胞的修复机制；肺内输入 Notch1 诱导性 MSCs，研究其对受损气道上皮细胞、Ⅱ型肺泡上皮细胞的修复机制及全身慢性炎症的影响。为诱导性 MSCs 治疗 COPD 提供理论和实验基础。

Notch signaling pathway plays a vital role in development and differentiation in lung epithelial cells. It's also involved in mesenchymal stem cells(MSCs) function. we previously demonstrated that Notch signaling modulated MSCs self-regeneration and differentiation. In COPD rat models, Notch signaling down-regulated in airway epithelial cells and aveolar epithelial cells type Ⅱ. In this study, we attempt to determine Notch1 signaling regulating and preserving MSCs function of self-regeneration and differentiation. In vitro experiments, MSCs overexpressed with Notch1 cocultured with airway epithelial cells or aveolar epithelial cells will be performed and determine whether MSCs can recovery epithelial cells. In vivo experiments, we emphasize on whether Notch1-overexpressed MSCs infusion can repair the lung tissue and alleviate the inflammatory reaction. Taken together, we expect our achievements will throw light on the therapy of COPD.