2012-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649392摘要：因為在我們利用這些條件式基因剔除鼠完成研究Notch訊息是如何影響發育中呼吸道上皮的命運與分化，和在成鼠的呼吸道上皮是如何維持其恆定，並因此刊登了兩篇Development的文章後，我們又有另一個重要的發現，即是Notch訊息對肺泡的發育極為重要。這個發現不只在基礎研究上很令人感興趣，同時在臨床上更有其應用價值。因為肺泡的發育不良正是臨床病例最多且最難治療的慢性肺疾病-慢性阻塞性肺疾病簡稱肺氣腫的病理表徵。我們發現這個肺泡發育不良是在肺泡發育的過程中出問題，缺乏Notch訊息會導致和肺泡發育相關的基因-PDGF-A的表現量降低，進而影響和肺泡隔間相關的肺泡肌肉纖維母細胞(alveolar myofibroblast)的形成有關，最後造成飛泡發育不良。我們希望藉著完成相關之研究，不但可以完成另一篇優秀的論文，同時也有機會發展成另一個疾病的動物模式，並經由了解肺泡發育的基轉，進一步找出預防或治療肺泡發育不良或肺氣腫的方法。<br> Abstract: Previously, we have found that Notch signaling is required for Clara cell formation and maintenance. We have two papers published in Development. Now, we have a new finding that Notch signaling is required for normal alveolarization. This finding is very important because this phenotype is the main characteristic for chronic obstructive pulmonary disease (COPD) and bronchopulmonary dysplasia (BPD) of premature infants. This poor alveolarization appeared in the early stage of alveolar development. We found that loss of Notch signaling resulted in downregulating PDGF-A expression which is essential for alveolarization. Dwonregulation of PDGF-A leaded to disrupting the alveolar myofibroblast differentiation and, finally, caused poor alveolarization. We hope we can finish this project and elucidate its mechanism. We think we can use this mouse as a novel BPD or COPD animal model to study more about the mechanism of alveolarization, then we can have the chance to prevent or treat these important diseases.Notch肺泡形成血小板生長因子慢性肺疾病NotchalveloarizationPDGFchronic lung disease