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

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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.

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Acknowledgments

We thank T. Muratani for providing the SEC strain, and S. Nagao for technical assistance. We are also very grateful to H. Kogo, M. Taniguchi, T. Ohye, and H. Inagaki for their helpful discussions. This study was supported by a grant-in-aid for 21st Century COE program from the Ministry of Education, Science, Sports and Culture of Japan.

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Authors and Affiliations

  1. Department of Urology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan

    Manabu Ichino, Mamoru Kusaka, Yoko Kuroyanagi, Kiyohito Ishikawa, Ryoichi Shiroki & Kiyotaka Hoshinaga

  2. 21st Century COE program, Development Center for Targeted and Minimally Invasive Diagnosis and Treatment, Fujita Health University, Toyoake, Japan

    Manabu Ichino, Terumi Mori, Mamoru Kusaka, Yoko Kuroyanagi, Hiroe Kowa, Hiroki Kurahashi & Kiyotaka Hoshinaga

  3. Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan

    Terumi Mori, Hiroe Kowa & Hiroki Kurahashi

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  1. Manabu Ichino
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  2. Terumi Mori
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  3. Mamoru Kusaka
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  7. Hiroe Kowa
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  9. Kiyotaka Hoshinaga
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Correspondence to Manabu Ichino.

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Ichino, M., Mori, T., Kusaka, M. et al. Global gene expression profiling of renal scarring in a rat model of pyelonephritis. Pediatr Nephrol 23, 1059–1071 (2008). https://doi.org/10.1007/s00467-007-0717-6

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  • DOI: https://doi.org/10.1007/s00467-007-0717-6

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