Increased Urinary Neutrophil Gelatinase Associated Lipocalin Levels in a Rat Model of Upper Urinary Tract Infection

Manabu Ichino, Yoko Kuroyanagi, Mamoru Kusaka, Terumi Mori, Kiyohito Ishikawa, Ryoichi Shiroki, Hiroki Kurahashi, Kiyotaka Hoshinaga

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Purpose: Recurrent upper urinary tract infection is a common complication of vesicoureteral reflux that often leads to irreversible renal scarring. In our previous study of a rat model of renal bacterial infection we performed global gene expression profiling of the kidney during the onset of renal scarring. We have further investigated the product of an up-regulated gene product, NGAL, in this animal model to evaluate its potential usefulness as a biomarker of renal scarring. Materials and Methods: Renal NGAL mRNA and protein levels were examined by real-time polymerase chain reaction, Western blot and immunohistochemistry. Urinary NGAL levels were monitored by direct enzyme-linked immunosorbent assay. Results: Rat renal NGAL mRNA and protein levels were found to be increased soon after bacterial injection. They then decreased rapidly but subsequently persisted at high levels until the 6-week time point after injection. On histological analysis we found that NGAL protein was overproduced in macrophages and renal tubular cells 2 weeks after injection. However, renal tubular cells continued to produce NGAL 6 weeks after injection, whereas this expression was lost in infiltrating cells. Rat urinary NGAL levels were also markedly increased at the early stages of infection and they persisted at high levels throughout the latter stages of the experiment. Conclusions: Urinary NGAL may be a potential noninvasive diagnostic biomarker of renal scarring.

Original languageEnglish
Pages (from-to)2326-2331
Number of pages6
JournalJournal of Urology
Volume181
Issue number5
DOIs
Publication statusPublished - 01-05-2009

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Urinary Tract Infections
Kidney
Cicatrix
Injections
Biomarkers
Lipocalin-2
Vesico-Ureteral Reflux
Messenger RNA
Gene Expression Profiling
Bacterial Infections
Real-Time Polymerase Chain Reaction
Animal Models
Western Blotting
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Macrophages
Infection

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Ichino, M., Kuroyanagi, Y., Kusaka, M., Mori, T., Ishikawa, K., Shiroki, R., ... Hoshinaga, K. (2009). Increased Urinary Neutrophil Gelatinase Associated Lipocalin Levels in a Rat Model of Upper Urinary Tract Infection. Journal of Urology, 181(5), 2326-2331. https://doi.org/10.1016/j.juro.2009.01.010
Ichino, Manabu ; Kuroyanagi, Yoko ; Kusaka, Mamoru ; Mori, Terumi ; Ishikawa, Kiyohito ; Shiroki, Ryoichi ; Kurahashi, Hiroki ; Hoshinaga, Kiyotaka. / Increased Urinary Neutrophil Gelatinase Associated Lipocalin Levels in a Rat Model of Upper Urinary Tract Infection. In: Journal of Urology. 2009 ; Vol. 181, No. 5. pp. 2326-2331.
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abstract = "Purpose: Recurrent upper urinary tract infection is a common complication of vesicoureteral reflux that often leads to irreversible renal scarring. In our previous study of a rat model of renal bacterial infection we performed global gene expression profiling of the kidney during the onset of renal scarring. We have further investigated the product of an up-regulated gene product, NGAL, in this animal model to evaluate its potential usefulness as a biomarker of renal scarring. Materials and Methods: Renal NGAL mRNA and protein levels were examined by real-time polymerase chain reaction, Western blot and immunohistochemistry. Urinary NGAL levels were monitored by direct enzyme-linked immunosorbent assay. Results: Rat renal NGAL mRNA and protein levels were found to be increased soon after bacterial injection. They then decreased rapidly but subsequently persisted at high levels until the 6-week time point after injection. On histological analysis we found that NGAL protein was overproduced in macrophages and renal tubular cells 2 weeks after injection. However, renal tubular cells continued to produce NGAL 6 weeks after injection, whereas this expression was lost in infiltrating cells. Rat urinary NGAL levels were also markedly increased at the early stages of infection and they persisted at high levels throughout the latter stages of the experiment. Conclusions: Urinary NGAL may be a potential noninvasive diagnostic biomarker of renal scarring.",
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Ichino, M, Kuroyanagi, Y, Kusaka, M, Mori, T, Ishikawa, K, Shiroki, R, Kurahashi, H & Hoshinaga, K 2009, 'Increased Urinary Neutrophil Gelatinase Associated Lipocalin Levels in a Rat Model of Upper Urinary Tract Infection', Journal of Urology, vol. 181, no. 5, pp. 2326-2331. https://doi.org/10.1016/j.juro.2009.01.010

Increased Urinary Neutrophil Gelatinase Associated Lipocalin Levels in a Rat Model of Upper Urinary Tract Infection. / Ichino, Manabu; Kuroyanagi, Yoko; Kusaka, Mamoru; Mori, Terumi; Ishikawa, Kiyohito; Shiroki, Ryoichi; Kurahashi, Hiroki; Hoshinaga, Kiyotaka.

In: Journal of Urology, Vol. 181, No. 5, 01.05.2009, p. 2326-2331.

Research output: Contribution to journalArticle

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T1 - Increased Urinary Neutrophil Gelatinase Associated Lipocalin Levels in a Rat Model of Upper Urinary Tract Infection

AU - Ichino, Manabu

AU - Kuroyanagi, Yoko

AU - Kusaka, Mamoru

AU - Mori, Terumi

AU - Ishikawa, Kiyohito

AU - Shiroki, Ryoichi

AU - Kurahashi, Hiroki

AU - Hoshinaga, Kiyotaka

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N2 - Purpose: Recurrent upper urinary tract infection is a common complication of vesicoureteral reflux that often leads to irreversible renal scarring. In our previous study of a rat model of renal bacterial infection we performed global gene expression profiling of the kidney during the onset of renal scarring. We have further investigated the product of an up-regulated gene product, NGAL, in this animal model to evaluate its potential usefulness as a biomarker of renal scarring. Materials and Methods: Renal NGAL mRNA and protein levels were examined by real-time polymerase chain reaction, Western blot and immunohistochemistry. Urinary NGAL levels were monitored by direct enzyme-linked immunosorbent assay. Results: Rat renal NGAL mRNA and protein levels were found to be increased soon after bacterial injection. They then decreased rapidly but subsequently persisted at high levels until the 6-week time point after injection. On histological analysis we found that NGAL protein was overproduced in macrophages and renal tubular cells 2 weeks after injection. However, renal tubular cells continued to produce NGAL 6 weeks after injection, whereas this expression was lost in infiltrating cells. Rat urinary NGAL levels were also markedly increased at the early stages of infection and they persisted at high levels throughout the latter stages of the experiment. Conclusions: Urinary NGAL may be a potential noninvasive diagnostic biomarker of renal scarring.

AB - Purpose: Recurrent upper urinary tract infection is a common complication of vesicoureteral reflux that often leads to irreversible renal scarring. In our previous study of a rat model of renal bacterial infection we performed global gene expression profiling of the kidney during the onset of renal scarring. We have further investigated the product of an up-regulated gene product, NGAL, in this animal model to evaluate its potential usefulness as a biomarker of renal scarring. Materials and Methods: Renal NGAL mRNA and protein levels were examined by real-time polymerase chain reaction, Western blot and immunohistochemistry. Urinary NGAL levels were monitored by direct enzyme-linked immunosorbent assay. Results: Rat renal NGAL mRNA and protein levels were found to be increased soon after bacterial injection. They then decreased rapidly but subsequently persisted at high levels until the 6-week time point after injection. On histological analysis we found that NGAL protein was overproduced in macrophages and renal tubular cells 2 weeks after injection. However, renal tubular cells continued to produce NGAL 6 weeks after injection, whereas this expression was lost in infiltrating cells. Rat urinary NGAL levels were also markedly increased at the early stages of infection and they persisted at high levels throughout the latter stages of the experiment. Conclusions: Urinary NGAL may be a potential noninvasive diagnostic biomarker of renal scarring.

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