Effect of Airway Microenvironment on TGF-beta driven Epithelial to Mesenchymal Cell Transition in the Transplanted Lung

一些死于肺病的病人很幸运地通过肺移植获得了新生。不幸的是，他们中的一半人会在移植后的5年内死亡，因为他们的新肺衰竭了。新生的肺被阻塞小支气管的瘢痕过程所破坏。这个过程被称为闭塞性细支气管炎或OB。我们将试图找出肺支气管的内衬细胞（称为上皮细胞）在OB的发生中是否至关重要。受损的内衬细胞通常在健康个体中得到修复。然而，如果损伤频繁或持续，这些细胞可以改变它们的行为，成为专门的疤痕细胞（称为间充质细胞）。间充质细胞负责疤痕组织的沉积。我们将测试肺移植后对衬里细胞的反复损伤是否会使它们变成专门的细胞，并沉积疤痕组织，从而阻塞小支气管。在这项研究中，我们将从接受肺移植的患者身上提取衬里细胞，并在实验室中培养它们。然后，我们将研究肺部的生长因子与受伤时释放的危险信号是否能驱动从衬里细胞到瘢痕细胞的变化。这很重要，因为如果我们了解这种变化是如何发生的，就有可能阻止它，防止衬里细胞改变行为。希望是开发新的治疗方法来保护支气管免受疤痕。这将大大提高接受过肺移植的患者的长期生存率。

Some patients dying of lung disease are lucky enough to get a new lease of life with a lung transplant. Tragically, half of them will die within 5 years of having their transplant because their new lungs fail. The new lungs are destroyed by a scarring process which blocks the small bronchial tubes. This process is called obliterative bronchiolitis or OB. We will try to find out if the lining cells of the lungs’ bronchial tubes, (called epithelial cells), are vital in developing OB. Damaged lining cells are normally repaired in healthy individuals. However, if the damage is frequent or continuous, these cells can change their behaviour to become specialist scarring cells (called mesenchymal cells). Mesenchymal cells are responsible for depositing scar tissue. We will test if repeated damage to the lining cells after lung transplant makes them change into specialist cells which deposit scar tissue which could block the small bronchial tubes. In this study, we will take lining cells from patients who have had a lung transplant and grow them in the laboratory. We will then investigate if growth factors in the lung when combined with danger signals released at times of injury can drive the change from lining cells to scarring cells. This is important because if we understand how this change occurs, it may be possible to block it and prevent lining cells from changing behaviour. The hope would be to develop new treatments which protect the bronchial tubes from scarring. This would greatly improve long term survival in patients who have had a lung transplant.