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 fi-
brosis, 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.