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iRhom2 and TNF: Partners or enemies?
Marina Badenes1, Colin Adrain1,2
1Instituto Gulbenkian de Ciência (IGC), Oeiras, Portugal. mbadenes@igc.gulbenkian.pt cadrain@igc.gulbenkian.pt.
Science Signaling
|October 31, 2019
Summary
iRhom2 protects against liver fibrosis by regulating TNF receptor shedding. This study reveals iRhom2
Area of Science:
- Cell biology
- Molecular medicine
- Gastroenterology
Background:
- iRhom2 is a cofactor for ADAM17, a metalloprotease involved in shedding TNF-α and TNFRs.
- Dysregulated TNF receptor signaling contributes to liver fibrosis.
Purpose of the Study:
- To investigate the role of iRhom2 in liver fibrosis.
- To elucidate the mechanism by which iRhom2 influences TNFR shedding in hepatic stellate cells.
Main Methods:
- Cell culture of hepatic stellate cells.
- Analysis of ADAM17-mediated protein shedding.
- Assessment of TNFR signaling pathways.
- In vivo models of liver injury and fibrosis.
Main Results:
- iRhom2 promotes ADAM17-mediated shedding of TNFRs in hepatic stellate cells.
- Reduced TNFR signaling was observed due to iRhom2-dependent shedding.
- iRhom2 demonstrated a protective role against liver fibrosis in response to injury.
Conclusions:
- iRhom2 plays a critical protective role in mitigating liver fibrosis.
- Targeting the iRhom2-ADAM17 axis may offer a therapeutic strategy for liver fibrosis.
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