Molecular mechanisms of reduced expression of the angiostatic chemokine IP-10 in idiopathic pulmonary fibrosis

特发性肺纤维化血管抑制趋化因子 IP-10 表达减少的分子机制

• 批准号: G0600890/1
• 负责人: Linhua Pang
• 金额: $ 35.8万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600890%2F1
• 关键词: Molecular; mechanisms; reduced; expression; angiostatic

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disorder characterised by irreversible scarring of the lung and has no effective therapy. Excessive fibroblast (a cell type) growth and scar formation are the most important features of the disease and require new blood vessel formation to accommodate the nutritional need. In normal lung the new blood vessel formation is inhibited by an inhibitor protein called IP-10. However, in IPF lung, IP-10 production is reduced, leading to new blood vessel formation and unopposed fibroblast growth and scar formation. Why IP-10 expression is faulty in IPF lung is unclear and is an important area to study. We believe that key processes in IP-10 expression are defective in IPF. In the studies proposed here we will compare fibroblasts from IPF patients with normal cells to examine the molecular mechanisms regulating the IP-10 expression and identify the defective processes in IPF. This will help us to understand the disease better and may lead to the development of approaches to restore IP-10 expression as a new treatment for IPF.

特发性肺纤维化（IPF）是一种进行性、致命性肺部疾病，其特征是肺部不可逆转的疤痕，并且没有有效的治疗方法。成纤维细胞（一种细胞类型）过度生长和疤痕形成是该疾病最重要的特征，需要形成新的血管来满足营养需求。在正常肺部，新血管的形成受到一种名为 IP-10 的抑制剂蛋白的抑制。然而，在 IPF 肺部，IP-10 的产生减少，导致新血管形成、成纤维细胞生长不受阻碍和疤痕形成。为什么 IP-10 在 IPF 肺中表达有缺陷尚不清楚，这是一个需要研究的重要领域。我们认为 IPF 中 IP-10 表达的关键过程存在缺陷。在此提出的研究中，我们将比较 IPF 患者的成纤维细胞与正常细胞，以检查调节 IP-10 表达的分子机制并识别 IPF 中的缺陷过程。这将有助于我们更好地了解这种疾病，并可能导致开发恢复 IP-10 表达的方法，作为 IPF 的新治疗方法。