Reduction of renal fibrosis as a result of liposome encapsulated clodronate induced macrophage depletion after unilateral ureteral obstruction in rats

Su Ah Sung, Sang Kyung Jo, Won Yong Cho, Nam Hee Won, Hyoung Kyu Kim

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56 Citations (Scopus)

Abstract

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 osteopontin expression was also reduced by pretreatment with LC. Conclusion: Initial interstitial infiltration of macrophages contributes to tubulointerstitial fibrosis in UUO.

Original languageEnglish
JournalNephron - Experimental Nephrology
Volume105
Issue number1
DOIs
Publication statusPublished - 2006 Dec 1

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Clodronic Acid
Ureteral Obstruction
Liposomes
Fibrosis
Macrophages
Kidney
Osteopontin
Intravenous Injections
Transforming Growth Factor beta
Messenger RNA

Keywords

  • Liposome-encapsulated clodronate
  • Macrophages
  • Renal fibrosis
  • Unilateral ureteral obstruction

ASJC Scopus subject areas

  • Nephrology

Cite this

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title = "Reduction of renal fibrosis as a result of liposome encapsulated clodronate induced macrophage depletion after unilateral ureteral obstruction in rats",
abstract = "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 osteopontin expression was also reduced by pretreatment with LC. Conclusion: Initial interstitial infiltration of macrophages contributes to tubulointerstitial fibrosis in UUO.",
keywords = "Liposome-encapsulated clodronate, Macrophages, Renal fibrosis, Unilateral ureteral obstruction",
author = "Sung, {Su Ah} and Jo, {Sang Kyung} and Cho, {Won Yong} and Won, {Nam Hee} and Kim, {Hyoung Kyu}",
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T1 - Reduction of renal fibrosis as a result of liposome encapsulated clodronate induced macrophage depletion after unilateral ureteral obstruction in rats

AU - Sung, Su Ah

AU - Jo, Sang Kyung

AU - Cho, Won Yong

AU - Won, Nam Hee

AU - Kim, Hyoung Kyu

PY - 2006/12/1

Y1 - 2006/12/1

N2 - 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 osteopontin expression was also reduced by pretreatment with LC. Conclusion: Initial interstitial infiltration of macrophages contributes to tubulointerstitial fibrosis in UUO.

AB - 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 osteopontin expression was also reduced by pretreatment with LC. Conclusion: Initial interstitial infiltration of macrophages contributes to tubulointerstitial fibrosis in UUO.

KW - Liposome-encapsulated clodronate

KW - Macrophages

KW - Renal fibrosis

KW - Unilateral ureteral obstruction

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