Small molecule inhibitors and primary airway fibroblast activation in severe asthma

小分子抑制剂和严重哮喘中初级气道成纤维细胞活化

• 批准号: G0800753/1
• 负责人: Peter Howarth
• 金额: $ 5.67万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0800753%2F1
• 关键词: Small; molecule; inhibitors; primary; airway

Asthma is a common and disabling problem for many, particularly those with severe persistent disease that prevents them living a normal life. In these individuals the disease leads to a progressive decline in lung function despite standard asthma therapies and the airways are left permanently impaired. Our research has shown that this can be linked to scarring within the airway wall. Such scarring is due to the deposition of collagen from activated cells called fibroblasts. This research has also demonstrated that fibroblasts, grown in the laboratory from small samples of the airway lining tissue (biopsies), from patient volunteers with severe asthma generate more collagen than do fibroblasts grown from biopsies obtained from the airways of either healthy non-asthmatic volunteers or volunteers with mild asthma. Additional studies have suggested that specific intracellular signalling pathways may be involved in this altered response. This industrial collaboration with UCB Celltech provides access to small molecule pathway inhibitors that allow the undertanding of the relevance of these pathways to the altered synthetic function of these fibroblasts. Through this better understanding it will be possible to target specific disease processes that hopefully will lead to novel therapies that in the future will prevent the progressive decline in lung function in asthma

哮喘对许多人来说是一种常见的致残性问题，特别是那些患有严重持续性疾病的人，这些疾病使他们无法过正常的生活。在这些个体中，尽管有标准的哮喘治疗，但该疾病导致肺功能进行性下降，并且气道永久受损。我们的研究表明，这可能与气道壁内的疤痕有关。这种瘢痕形成是由于胶原蛋白从被称为成纤维细胞的活化细胞中沉积。这项研究还表明，在实验室中从患有严重哮喘的患者志愿者的气道衬里组织（活检）的小样本中生长的成纤维细胞比从健康的非哮喘志愿者或患有轻度哮喘的志愿者的气道获得的活检中生长的成纤维细胞产生更多的胶原蛋白。其他研究表明，特定的细胞内信号通路可能参与这种改变的反应。与UCB Celltech的这种工业合作提供了获得小分子途径抑制剂的途径，这些抑制剂允许了解这些途径与这些成纤维细胞合成功能改变的相关性。通过这种更好的理解，将有可能靶向特定的疾病过程，有望导致新的治疗方法，在未来将防止哮喘肺功能的进行性下降