Aberrant signalling through gp130 in the pathogenesis of fibrotic lung diseases

纤维化肺疾病发病机制中 gp130 的异常信号传导

• 批准号: nhmrc : 303137
• 负责人: A/Pr Steven Mutsaers
• 金额: $ 30.44万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/aberrant-signalling-gp130-lung-diseases/98077
• 关键词: Aberrant; signalling; through; gp130; pathogenesis

Pulmonary fibrosis is a chronic diffuse interstitial lung disease of unknown cause, characterised pathologically by inflammation and fibrosis of the lung tissue. The prognosis is poor with a 50% mortality at five years after diagnosis and considerable morbidity during those years. Previous investigations have documented the role for inflammation in the development of pulmonary fibrosis and current therapeutic strategies are aimed at suppressing the inflammation. Data generated over the past decade also have established the concept that the molecular processes underlying the fibrogenesis component may represent a new opportunity for therapeutic intervention. Attempts to treat fibrosis have for the most part consisted of anti- inflammatory drugs, almost exclusively steroids. The effectiveness of steroids is variable and can be associated with significant side effects. This project will examine the effects of a family of molecules called cytokines that signal through gp130 as critical determinants of disease susceptibility and progression. gp 130 is a shared component in the receptor complexes for IL-6 family cytokines (IL-6, IL-11, LIF, OSM) which are important regulators of both the phenotype and proliferation of fibroblasts in health and in response to injury. Our data raises the possibility of developing pharmacological manipulators of gp130 signalling pathways that would suppress fibrosis but leave normal cellular defense mechanisms necessary for host defense in the lung intact.

肺纤维化是一种原因不明的慢性弥漫性间质性肺病，其病理特征为肺组织的炎症和纤维化。预后差，诊断后5年的死亡率为50%，在这些年中发病率相当高。以前的研究已经证明了炎症在肺纤维化发展中的作用，目前的治疗策略旨在抑制炎症。在过去十年中产生的数据也建立了这样一个概念，即纤维形成组分的分子过程可能代表了治疗干预的新机会。治疗纤维化的尝试大部分由抗炎药组成，几乎完全是类固醇。类固醇的有效性是可变的，可能与显着的副作用。该项目将研究一个称为细胞因子的分子家族的作用，这些分子通过gp 130发出信号，作为疾病易感性和进展的关键决定因素。gp 130是IL-6家族细胞因子（IL-6、IL-11、LIF、OSM）的受体复合物中的共有组分，所述细胞因子是健康和响应损伤的成纤维细胞的表型和增殖的重要调节剂。我们的数据提高了开发gp 130信号通路的药理学操纵器的可能性，这种操纵器将抑制纤维化，但保持肺中宿主防御所必需的正常细胞防御机制不变。