Related Experiment Video
Updated: May 2, 2026
Unilateral Ureteral Obstruction Model for Investigating Kidney Interstitial Fibrosis
Published on: April 25, 2025
Exaggerated renal fibrosis in P2X4 receptor-deficient mice following unilateral ureteric obstruction
Min Jeong Kim1, Clare M Turner2, Reiko Hewitt2
1Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College London, London, UK Clinic for Transplantations immunology and Nephrology, University Hospital Basel, Basel, Switzerland Department of Biomedicine, Molecular Nephrology, University Hospital Basel, Basel, Switzerland.
Background:
The ATP-sensitive P2X7 receptor (P2X7R) has been shown to contribute to renal injury in nephrotoxic nephritis, a rodent model of acute glomerulonephritis, and in unilateral ureteric obstruction (UUO), a rodent model of chronic interstitial inflammation and fibrosis. Renal tubular cells, endothelial cells and macrophages also express the closely related P2X4 receptor (P2X4R), which is chromosomally co-located with P2X7R and has 40% homology; it is also pro-inflammatory and has been shown to interact with P2X7R to modulate its pro-apoptotic and pro-inflammatory effects. Therefore, we chose to explore the function of P2X4R in the UUO model of renal injury using knockout mice. We hypothesized that UUO-induced tubulointerstitial damage and fibrosis would also be attenuated in P2X4R(-/-) mice.
Method:
P2X4R(-/-) and wild-type (WT) mice were subjected to either UUO or sham operation. Kidney samples taken on Days 7 and 14 were evaluated for renal inflammation and fibrosis, and expression of pro-fibrotic factors.
Results:
To our surprise, the obstructed kidney in P2X4R(-/-) mice showed more severe renal injury, more collagen deposition (picrosirius red staining, increase of 53%; P < 0.05) and more type I collagen staining (increase of 107%; P < 0.01), as well as increased mRNA for TGF-β (increase of 102%, P < 0.0005) and CTGF (increase of 157%; P < 0.05) by Day 14, compared with the UUO WT mice.
Conclusion:
These findings showed that lack of P2X4R expression leads to increased renal fibrosis, and increased expression of TGF-β and CTGF in the UUO model.
Insights
The ATP-sensitive P2X4 receptor (P2X4R) surprisingly exacerbates renal fibrosis in a mouse model of kidney injury. Lack of P2X4R leads to increased collagen deposition and pro-fibrotic factors, highlighting its protective role.
Area of Science:
- Nephrology
- Immunology
- Molecular Biology
Background:
- The ATP-sensitive P2X7 receptor (P2X7R) is implicated in renal injury.
- The P2X4 receptor (P2X4R), closely related to P2X7R, is also pro-inflammatory.
- P2X4R interacts with P2X7R, modulating its effects on apoptosis and inflammation.
Purpose of the Study:
- To investigate the role of P2X4R in unilateral ureteric obstruction (UUO)-induced kidney injury.
- To determine if P2X4R knockout mice exhibit attenuated renal damage and fibrosis in the UUO model.
Main Methods:
- Unilateral ureteric obstruction (UUO) or sham surgery was performed on P2X4R knockout and wild-type mice.
- Kidney tissues were analyzed for inflammation, fibrosis, and pro-fibrotic factor expression at Days 7 and 14.
Main Results:
- P2X4R knockout mice showed significantly increased renal injury and collagen deposition compared to wild-type mice.
- mRNA levels of TGF-β and CTGF were markedly elevated in the obstructed kidneys of P2X4R knockout mice.
- These findings contradict the initial hypothesis, indicating a protective role for P2X4R.
Conclusions:
- Absence of P2X4R expression exacerbates renal fibrosis in the UUO model.
- P2X4R deficiency leads to increased expression of key pro-fibrotic factors, TGF-β and CTGF.
- P2X4R plays a protective role in mitigating kidney fibrosis.
