Journal
NEPHRON EXPERIMENTAL NEPHROLOGY
Volume 105, Issue 1, Pages E1-E9Publisher
KARGER
DOI: 10.1159/000096859
Keywords
liposome-encapsulated clodronate; macrophages; unilateral ureteral obstruction; renal fibrosis
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Background/Aim: Macrophages have been thought to play a role in renal tubulointerstitial fibrosis; recent reports have demonstrated an antifibrotic effect of macrophages in late-stage renal fibrosis. Liposome-encapsulated clodronate (LC) produces a selective and systemic depletion of phagocytic macrophages in vivo. To study the role of initial infiltrating macrophages in renal fibrosis, we compared the effects of pretreatment with LC and a liposome vehicle for control of the severity of renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. Methods: One day after a single intravenous injection of LC or liposome vehicle, the rats underwent UUO. Following 1, 5, and 14 days, the kidneys were examined to evaluate macrophage infiltration and renal fibrosis. Results: LC depleted macrophages systemically and reduced renal fibrosis associated with UUO; this beneficial effect was accompanied by a decrease of transforming growth factor beta mRNA expression. The osteopontinex-pression was also reduced by pretreatment with LC. Conclusion: Initial interstitial infiltration of macrophages contributes to tubulointerstitial fibrosis in UUO. Copyright (c) 2007 S. Karger AG, Basel.
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