TRPA1; a potential therapeutic target in idiopathic pulmonary fibrosis

点击翻译按钮获取中文摘要

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 persistent cough, become extremely breathless, and finally die as a result of lung failure. The cause of IPF is unknown. Only two treatments are available, but these are not very effective, and produce frequent and unpleasant side effects. 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. All cells contain proteins called ion channels that conduct ions such as calcium into the cell. We have identified an ion channel called TRPA1 in human lung myofibroblasts, and believe that this is a key signalling molecule through which myofibroblasts generate scar tissue. We will test this hypothesis in this proposal, and if we are correct, we expect that blocking TRPA1 will slow or halt the progress of IPF. Drugs that block TRPA1 are already being studied in other diseases, and to-date, have been well tolerated by patients. We therefore expect that the results from our study will provide a strong rationale for the assessment of TRPA1 blockers in clinical trials for patients with IPF.