title: Global gene expression profiling of renal scarring in a rat model of pyelonephritis.
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)-1beta, transforming growth factor (TGF)-beta, 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.
authors.affiliation: Department of Urology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, Japan. michino@fujita-hu.ac.jp
authors.forename: Manabu
authors.initials: M
authors.lastname: Ichino
authors.forename: Terumi
authors.initials: T
authors.lastname: Mori
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kusaka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kuroyanagi
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Shiroki
authors.forename: Hiroe
authors.initials: H
authors.lastname: Kowa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurahashi
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Hoshinaga
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D004926:Escherichia coli; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks; D007668:Kidney / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011704:Pyelonephritis / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D015415:Biomarkers