Role of tumor necrosis factor-alpha and iRhoms in liver damage and regeneration (A17)

肿瘤坏死因子-α 和 iRhoms 在肝损伤和再生中的作用 (A17)

• 批准号: 290204773
• 金额: --
• 依托单位: Institut für Molekulare Medizin II
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/290204773?language=en
• 关键词: Role; tumor; necrosis; factor; alpha

The project will investigate the role of iRhoms and TNF modulators during liver damage and regeneration. Previous findings identified a role for iRhom2 during TACE/ADAM17 maturation and hence modulating TNF signalling. We uncovered however, that absence of iRhom2 promoted liver fibrosis by preventing shedding of TNFR and thereby increasing TNF signalling during bile duct ligation. Preliminary data uncovers a critical role for iRhom1 during liver fibrosis with unchanged presence of mature TACE/ADAM17. Further preliminary data hints to a substantial role of iRhom2 during liver regeneration, possibly dependent on TNF production. Moreover, the RNA binding protein FMR1 has been identified as TNF modulator. Accordingly, the project A17 will investigate the roles of iRhom1, iRhom2, and the TNF modulator FMR1 during liver damage and regeneration.

该项目将研究iRhoms和TNF调节剂在肝损伤和再生中的作用。先前的研究结果确定了iRhom2在TACE/ADAM17成熟过程中的作用，从而调节TNF信号传导。然而，我们发现iRhom2的缺失通过阻止TNFR的脱落，从而在胆管结痂过程中增加TNF信号传导，从而促进肝纤维化。初步数据揭示了成熟TACE/ADAM17不变的情况下，iRhom1在肝纤维化中的关键作用。进一步的初步数据提示iRhom2在肝脏再生中的重要作用，可能依赖于TNF的产生。此外，RNA结合蛋白FMR1已被确定为TNF调节剂。因此，A17项目将研究iRhom1、iRhom2和TNF调节剂FMR1在肝损伤和再生中的作用。