Altered gp130-mediated signalling in the regulation of pulmonary fibrosis

改变 gp130 介导的信号传导以调节肺纤维化

• 批准号: nhmrc : 458703
• 负责人: A/Pr Steven Mutsaers
• 金额: $ 24.94万
• 依托单位: The University of Western Australia
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/altered-gp130-mediated-pulmonary-fibrosis/95288
• 关键词: Altered; gp130; mediated; signalling; regulation

Pulmonary fibrosis is a chronic diffuse interstitial lung disease often 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 using anti- inflammatory drugs, almost exclusively steroids. The effectiveness of steroids is variable although generally poor and can be associated with significant side effects suggesting that other approaches need to be considered. Data generated over the past decade also have established the concept that the molecular processes underlying the development of fibrosis may represent a new opportunity for therapeutic intervention. This project will build on previous studies examining 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 and can signal down two major pathways. We have shown that the development of lung fibrosis depends on which specific signalling pathway is used. This study will determine how fibrosis is controlled by these pathways. 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.

肺纤维化是一种慢性弥漫性间质性肺病，通常病因不明，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。先前的研究已经记录了炎症在肺纤维化发展中的作用，并且当前的治疗策略旨在使用抗炎药物（几乎完全是类固醇）来抑制炎症。类固醇的有效性是可变的，尽管通常很差，并且可能与显着的副作用有关，这表明需要考虑其他方法。过去十年中产生的数据也确立了纤维化发展的分子过程可能代表治疗干预的新机会的概念。这个项目将建立在以前的研究上，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家族细胞因子的受体复合物中的共有组分，并且可以向两个主要途径发出信号。我们已经表明，肺纤维化的发展取决于使用哪种特定的信号通路。这项研究将确定纤维化是如何通过这些途径控制的。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。