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

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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.