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 journalArticlepeer-review

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 - 07-2008

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

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