Global gene expression profiling of renal scarring in a rat model of pyelonephritis

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Renal scarring is a serious complication of chronic pyelonephritis that occurs due to vesicoureteral reflux. In our study, we performed global expression profiling of the kidney during renal scarring formation in a rat pyelonephritis model. An inoculum of Escherichia coli was injected directly into the renal cortex. Histologically, renal scarring developed during the 3-to-4 week period after injection. The time-course expression profile of 18,442 genes was then analyzed using microarrays, followed by validation with real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Most of the genes found to be up-regulated during renal scarring are associated with immune and defense responses, including cytokines, chemokines and their receptors, complement factors, adhesion molecules and extracellular matrix proteins. These genes were up-regulated as early as 1 week after injection, when no fibrotic changes were yet evident, peaked at 2 weeks, and gradually decreased thereafter. However, a subset of cytokine genes was found to be persistently activated even at 6 weeks after injection, including interleukin (IL)-1β, transforming growth factor (TGF)-β, and IL-3. Further statistical analysis indicated that the pathways mediated by these cytokines are activated concomitantly with renal scarring formation. The products of these genes may thus potentially be novel non-invasive diagnostic or prognostic biomarkers of renal scarring.

Original languageEnglish
Pages (from-to)1059-1071
Number of pages13
JournalPediatric Nephrology
Volume23
Issue number7
DOIs
Publication statusPublished - 01-07-2008

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Pyelonephritis
Gene Expression Profiling
Cicatrix
Kidney
Genes
Cytokines
Injections
Vesico-Ureteral Reflux
Chemokine Receptors
Interleukin-3
Extracellular Matrix Proteins
Transforming Growth Factors
Reverse Transcriptase Polymerase Chain Reaction
Interleukin-1
Real-Time Polymerase Chain Reaction
Biomarkers
Escherichia coli

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

Cite this

Ichino, M., Mori, T., Kusaka, M., Kuroyanagi, Y., Ishikawa, K., Shiroki, R., ... Hoshinaga, K. (2008). Global gene expression profiling of renal scarring in a rat model of pyelonephritis. Pediatric Nephrology, 23(7), 1059-1071. https://doi.org/10.1007/s00467-007-0717-6
Ichino, Manabu ; Mori, Terumi ; Kusaka, Mamoru ; Kuroyanagi, Yoko ; Ishikawa, Kiyohito ; Shiroki, Ryoichi ; Kowa, Hiroe ; Kurahashi, Hiroki ; Hoshinaga, Kiyotaka. / Global gene expression profiling of renal scarring in a rat model of pyelonephritis. In: Pediatric Nephrology. 2008 ; Vol. 23, No. 7. pp. 1059-1071.
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Ichino, M, Mori, T, Kusaka, M, Kuroyanagi, Y, Ishikawa, K, Shiroki, R, Kowa, H, Kurahashi, H & Hoshinaga, K 2008, 'Global gene expression profiling of renal scarring in a rat model of pyelonephritis', Pediatric Nephrology, vol. 23, no. 7, pp. 1059-1071. https://doi.org/10.1007/s00467-007-0717-6

Global gene expression profiling of renal scarring in a rat model of pyelonephritis. / Ichino, Manabu; Mori, Terumi; Kusaka, Mamoru; Kuroyanagi, Yoko; Ishikawa, Kiyohito; Shiroki, Ryoichi; Kowa, Hiroe; Kurahashi, Hiroki; Hoshinaga, Kiyotaka.

In: Pediatric Nephrology, Vol. 23, No. 7, 01.07.2008, p. 1059-1071.

Research output: Contribution to journalArticle

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AU - Ichino, Manabu

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AU - Hoshinaga, Kiyotaka

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AB - Renal scarring is a serious complication of chronic pyelonephritis that occurs due to vesicoureteral reflux. In our study, we performed global expression profiling of the kidney during renal scarring formation in a rat pyelonephritis model. An inoculum of Escherichia coli was injected directly into the renal cortex. Histologically, renal scarring developed during the 3-to-4 week period after injection. The time-course expression profile of 18,442 genes was then analyzed using microarrays, followed by validation with real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Most of the genes found to be up-regulated during renal scarring are associated with immune and defense responses, including cytokines, chemokines and their receptors, complement factors, adhesion molecules and extracellular matrix proteins. These genes were up-regulated as early as 1 week after injection, when no fibrotic changes were yet evident, peaked at 2 weeks, and gradually decreased thereafter. However, a subset of cytokine genes was found to be persistently activated even at 6 weeks after injection, including interleukin (IL)-1β, transforming growth factor (TGF)-β, and IL-3. Further statistical analysis indicated that the pathways mediated by these cytokines are activated concomitantly with renal scarring formation. The products of these genes may thus potentially be novel non-invasive diagnostic or prognostic biomarkers of renal scarring.

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Ichino M, Mori T, Kusaka M, Kuroyanagi Y, Ishikawa K, Shiroki R et al. Global gene expression profiling of renal scarring in a rat model of pyelonephritis. Pediatric Nephrology. 2008 Jul 1;23(7):1059-1071. https://doi.org/10.1007/s00467-007-0717-6