Resolving mediators as novel therapies for idiopathic pulmonary fibrosis

特发性肺纤维化（IPF）是一种预后不良的常见疾病。所有诊断为IPF的患者中有一半将在3-4年内死亡。肺中发生瘢痕形成过程，最终用致密的瘢痕组织取代正常健康的肺组织，这阻止氧气进入血液和与呼吸相关的正常肺扩张。结果，患者出现顽固性咳嗽，变得极度呼吸困难，最终因肺衰竭而死亡。IPF的病因尚不清楚，没有影响这些患者预期寿命或生活质量的有效治疗。大量证据表明，称为肌成纤维细胞的细胞参与了IPF肺瘢痕组织的生成。这些细胞在正常的伤口愈合中很重要，并为包括肺在内的健康器官提供结构，但在疾病中它们表现异常。正是肌成纤维细胞产生填充肺部的致密组织。此外，它们移动到异常位置并繁殖，导致肌成纤维细胞和瘢痕组织的密集聚集，扭曲正常的肺结构。一组称为分解介质的化学物质是由身体对组织损伤做出反应而产生的，并使发炎的组织恢复到健康状态。基于在其他器官中的工作，以及我们自己研究人肺肌成纤维细胞的初步数据，我们认为这些分解介质也可能非常有效地抑制肺肌成纤维细胞的促瘢痕形成功能，从而减少IPF中的肺瘢痕形成过程。使用从健康受试者和IPF患者获得的人肺肌成纤维细胞以及肺组织，我们将研究分辨介质如何有效抑制导致肺瘢痕形成的肌成纤维细胞过程。

Idiopathic pulmonary fibrosis (IPF) is a common disease with a bleak prognosis. Half of all patients diagnosed with IPF will die within 3-4 years. A scarring process occurs in the lungs, eventually replacing normal healthy lung tissue with dense scar tissue which prevents oxygen passing into the blood and the normal lung expansion associated with breathing. As a result patients develop intractable cough, become extremely breathless, and finally die as a result of lung failure. The cause of IPF is unknown and there are no useful treatments which impact on either the life expectancy or quality of life of these patients. Considerable evidence implicates cells known as myofibroblasts in the generation of lung scar tissue in IPF. These cells are important in normal wound healing and provide structure to healthy organs including lungs, but in disease they behave abnormally. It is myofibroblasts that produce the dense tissue that fills the lungs. In addition they move to abnormal locations and multiply, leading to dense collections of myofibroblasts and scar tissue that distort normal lung structure. A group of chemicals called resolving mediators are produced by the body in response to tissue injury, and return inflamed tissues to the healthy state. Based on work in other organs, and our own preliminary data studying human lung myofibroblasts, we believe that these resolving mediators may also be very effective at inhibiting the pro-scarring function of lung myofibroblasts and hence reduce the lung scarring process in IPF. Using human lung myofibroblasts obtained from healthy subjects and patients with IPF, together with lung tissue, we will investigate how effective resolving mediators are at inhibiting the myofibroblast processes which lead to lung scarring.