RIPK3-deficient mice were not protected from nephrotoxic nephritis
N R Hill1, H T Cook2, C D Pusey3
1Renal and Vascular Inflammation Section, Hammersmith Hospital, 5N4 Commonwealth Building, W12 0NN, London, UK. nicola.hill1@imperial.ac.uk.
Background:
Necrotizing glomerular lesions are a feature of severe glomerulonephritis. Unlike apoptosis, cellular necrosis has the potential to release damage-associated proteins into the microenvironment, thereby potentiating inflammation. Until recently necrosis was thought to be an unregulated cellular response to injury. However, recent evidence suggests that under certain circumstances receptor mediated necrosis occurs in response to death ligand signalling, one form of which is termed necroptosis. RIPK3, a receptor interacting protein, is a limiting step in the intracellular signalling pathway of necroptosis. A non-redundant role for RIPK3 has been implicated in mouse models of renal ischaemia reperfusion injury and toxic renal injury. The aim of this study was to investigate the role of RIPK3 in nephrotoxic nephritis (NTN), a model of immune complex glomerulonephritis in mice.
Methods:
We induced NTN in RIPK3-/- and WT mice, comparing histology and renal function in both groups.
Results:
There was no improvement in urinary albumin creatinine ratio, serum urea, glomerular thrombosis or glomerular macrophage infiltration in the RIPK3-/- mice compared to WT. There was also no difference in number of apoptotic cells in glomeruli as measured by TUNEL staining between the RIPK3-/- and WT mice.
Conclusion:
The data suggests that RIPK3 is not on a critical pathway in the pathogenesis of nephrotoxic nephritis.
Insights
Receptor interacting protein 3 (RIPK3) does not play a critical role in nephrotoxic nephritis (NTN), a model of immune complex glomerulonephritis. Studies show RIPK3 deficiency did not alter disease severity or inflammation in mice.
Area of Science:
- Immunology
- Nephrology
- Cellular Biology
Background:
- Necrotizing glomerular lesions characterize severe glomerulonephritis.
- Necrosis releases damage-associated proteins, potentially worsening inflammation.
- Necroptosis, a form of regulated necrosis, is mediated by signaling pathways involving RIPK3.
Purpose of the Study:
- To investigate the role of RIPK3 in the pathogenesis of nephrotoxic nephritis (NTN).
- To determine if RIPK3 deficiency impacts immune complex glomerulonephritis development in a mouse model.
Main Methods:
- Nephrotoxic nephritis (NTN) was induced in RIPK3 knockout (RIPK3-/-) and wild-type (WT) mice.
- Histology and renal function were compared between RIPK3-/- and WT groups.
Main Results:
- No significant differences were observed in urinary albumin creatinine ratio, serum urea, glomerular thrombosis, or macrophage infiltration between RIPK3-/- and WT mice.
- TUNEL staining revealed no difference in glomerular apoptotic cell numbers between the groups.
Conclusions:
- RIPK3 is not a critical component in the pathogenic pathway of nephrotoxic nephritis.
- These findings suggest RIPK3 does not significantly influence immune complex glomerulonephritis in this model.
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